Mitochondrial cell death. Medical search. Frequent questions

Using cultured cells, the Washington University School of Medicine researchers found that the toxin MPP+ stopped the circulation of mitochondria in dopamine-producing cell axons, leading to the axonal withering and subsequently cell death. (genengnews.com)
Looking more closely at the mitochondria in treated cells, the researchers found that in some cases mitochondria seemed to be moving back toward the cell body, against the flow of other molecules and organelles, which suggested they were being trafficked back for repair. (genengnews.com)
Interestingly, the toxin had no effect on transportation of mitochondria in other types of nerve cells. (genengnews.com)
While the specificity for dopamine-producing neurons has still to be worked out, a clue may lie in the team's observation that in comparison with other types of nerve cells, mitochondria in this type of neuron are smaller in size and travel three times more slowly. (genengnews.com)
Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. (frontiersin.org)
More than just power houses of the cells ( 10 ), the role of mitochondria have been remarkably appreciated and revisited. (frontiersin.org)
Mitochondrial energetic adaptations encompass a plethora of conserved processes that maintain cell and organismal fitness and survival in the changing environment by adjusting the respiratory capacity of mitochondria. (nature.com)
For incomplete MOMP, mitochondrial membranes become permeable in most, but not all, the cell's mitochondria. (wikipedia.org)
In minority MOMP, only a few mitochondria of the cell experience MOMP-the result of sublethal stress. (wikipedia.org)
Although studies suggest that αSyn and its missense mutant, A53T, preferentially accumulate in the mitochondria, the mechanisms by which αSyn and mitochondrial proteins regulate each other to trigger mitochondrial and neuronal toxicity are poorly understood. (springer.com)
Despite these findings suggesting that mitochondria might be a key link between αSyn toxicity and neuronal degeneration in PD, the field still lacks an understanding of how αSyn abnormality and mitochondrial functional deficiency influence each other. (springer.com)
In addition to less ATP production and higher levels of reactive oxygen species, mitochondria in the brains of individuals with Alzheimer's disease show mitochondrial abnormalities that include altered shape, decreased density, and impaired respiration. (bmglabtech.com)
Altered mitochondrial dynamics, including excessive fission and fusion of mitochondria, also contribute to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
DESCRIPTION (provided by applicant): Mitochondria engage in multiple fundamental processes including biogenesis, fission/fusion, mitophagy, and cell death - in addition to their role as ATP generators in the cell. (elsevierpure.com)
Previous work in non-cardiac systems has shown that Parkin inhibits Bax translocation to mitochondria during cell death, but the mechanism has not been elucidated. (elsevierpure.com)
Most of the body's cells contain many mitochondria, and the mitochondria each contain many sets of mtDNA. (medlineplus.gov)
Furthermore, in AD brains, mitochondrially associated APP formed stable ∼480 kDa complexes with the translocase of the outer mitochondrial membrane 40 (TOM40) import channel and a super complex of ∼620 kDa with both mitochondrial TOM40 and the translocase of the inner mitochondrial membrane 23 (TIM23) import channel TIM23 in an "N in mitochondria -C out cytoplasm " orientation. (jneurosci.org)
Alterations in oxidative stress and glutathione-dependent redox-homeostasis were more pronounced in mitochondria compared to extra- mitochondrial cellular compartments. (uaeu.ac.ae)
Mitochondrial diseases affect the mitochondria, which are responsible for the body's energy. (mdlinx.com)
Jaya Ganesh, MD, an associate professor at the Department of Genetics and Genomic Sciences and director of the Mitochondrial Diseases program at the Icahn School of Medicine at Mount Sinai, explains that mitochondrial diseases affect the mitochondria, which are "the subcellular organelles important for energy production, ATP synthesis…and other functions, like regulating calcium, regulating the aging process, and managing certain reactive oxygen species. (mdlinx.com)
When the mitochondria fail, they can no longer convert food or oxygen into energy, resulting in cell injury and death. (mdlinx.com)
METHOD: Both genetic and functional alterations in mitochondria can lead to errors that trigger programmed cell death, which in turn give rise to a number of diseases that affect the nervous system. (lu.se)
6 Since brain cells have more mitochondria and more adenosine triphosphate consumption than the skin, the brain may have been affected at a different time than the skin with the hemodynamic changes that were induced during the study. (asahq.org)
Mitochondria play an important role in cell signaling, differentiation, and death. (asahq.org)
With the continuous worsening of cellular hypoxia, mitochondrial dysfunction becomes more apparent and may lead to decreased ability of the mitochondria to utilize oxygen that is reflected by the drop in mito-P o 2 . (asahq.org)
There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. (spandidos-publications.com)
Mitochondria are present in every cell except red blood cells. (msdmanuals.com)
Unlike other structures inside cells, mitochondria have some of their own genetic material that is inherited only from the mother. (msdmanuals.com)
Other genetic material for the mitochondria is in the cell nucleus with the rest of the cell's genetic material, and children with a disorder must inherit an abnormality from each parent. (msdmanuals.com)
Mitochondrial disorders cause mitochondria to stop working properly, so that less and less energy is generated within the cells. (msdmanuals.com)

Once triggered, it results in the diffusion of proteins from the space between the inner and outer mitochondrial membranes into the cytosol. (wikipedia.org)
The outer mitochondrial membrane, typically permeable to molecules smaller than 5 kDa, forms pores during MOMP that allow it to accommodate proteins larger than 100 kDa. (wikipedia.org)
Deficiency in ClpP induces an overload of mitochondrial misfolded/unfolded proteins, suppresses mitochondrial respiratory activity, increases mitochondrial oxidative damage and causes cell death. (springer.com)
Increased levels of reactive oxygen species can damage the molecular fabric of the cell including lipids, proteins, and DNA. (bmglabtech.com)
This can impair processes like mitochondrial transport and the clearance of proteins leading to bioenergetic deficits and neuronal dysfunction. (bmglabtech.com)
Further, by investigating the role of mitochondrial cell death proteins it was determined that a distinct approach will be required to improve kidney mitochondrial health in diabetes, due to their unique metabolic profile. (monash.edu)
Identification of proteins interacting with the mitochondrial small heat shock protein Hsp22 of Drosophila melanogaster: Implication in mitochondrial homeostasis. (nih.gov)
Expression of proteins on the ER-mitochondrial axis was increased by flufenoxuron. (korea.ac.kr)
Accumulation of APP across mitochondrial import channels, which varied with the severity of AD, inhibited the entry of nuclear-encoded cytochrome c oxidase subunits IV and Vb proteins, which was associated with decreased cytochrome c oxidase activity and increased levels of H 2 O 2 . (jneurosci.org)
This study involves precisely defining by molecular techniques the individual signaling proteins expressed in the acinar cell and then subsequently assessing if individual agonists utilize discrete and different elements of the PI-signaling pathway. (rochester.edu)
This may be related to mitochondrial proteins that regulate apoptosis and necrosis and that are shown to be induced in mouse fatty liver models. (medscape.com)
One of the CHE candidate proteins was LETM1, a protein that was initially characterized as the mitochondrial K + /H + exchanger (KHE). (vetmeduni.ac.at)
Truncated BID (tBID), a proapoptotic BCL2 family protein, induces BAK/BAX-dependent release of cytochrome c and other mitochondrial intermembrane proteins to the cytosol to induce apoptosis. (nih.gov)
In mammals and C. elegans , Bcl-2 family proteins facilitate apoptosis by regulating mitochondrial dynamics but do they play a similar role during apoptosis in Drosophila ? (biologists.com)
Thus, the researchers conclude, Bcl-2 family proteins do play a major role in controlling both mitochondrial dynamics and cell death in the Drosophila ovary. (biologists.com)
The contributors describe strategies for identifying and evaluating the biochemical and morphological changes that occur during apoptosis, autophagy, necrosis, and other forms of cell death, as well as for pinpointing the genes and proteins that may be involved. (cshlpress.com)
The most important enzymes involved in apoptosis are caspases, which hydrolyze important structural and functional proteins of the cell, ultimately leading to apoptosis. (spandidos-publications.com)
Once activated by their respective upstream signals, caspase-8 and -9 may cleave and activate downstream executioner caspases -3 and -7, which, in turn, cleave a plethora of target proteins, resulting in apoptotic death ( 6 - 8 ). (spandidos-publications.com)
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. (bvsalud.org)
The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. (bvsalud.org)
Our results indicate that several dozens of proteins for each cell type, are PE-lipoxidated in HT-22, MLE, and H9c2 cells and M2 macrophages after they were induced to undergo ferroptosis. (cdc.gov)
Pretreatment of cells with the strong nucleophile, 2-mercaptoethanol, prevented the formation of PE-lipoxidated proteins and blocked ferroptotic death. (cdc.gov)

Thus, mitochondrial adaptive cellular processes are important for physiological responses, including to nutrient availability, temperature and physical activity, and their failure leads to diseases associated with mitochondrial dysfunction such as metabolic and age-associated diseases and cancer. (nature.com)
Our previous studies on aspirin treated HepG2 cells strongly suggest cell cycle arrest and induction of apoptosis associated with mitochondrial dysfunction. (uaeu.ac.ae)

Here, we investigated whether this aberrant Cdk5 signalling contributes to the striatal neurodegeneration by altering mitochondrial dynamics processes. (bmj.com)

These changes can promote mitochondrial biogenesis and membrane dynamics that in turn support mitochondrial respiration. (nature.com)
Fig. 2: Transcriptional control of mitochondrial biogenesis through PGC1α. (nature.com)
Herein, we address the complex crosstalk that involves mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy, and cell death. (wellnessresources.com)
Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. (peerj.com)
Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. (peerj.com)
In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity. (peerj.com)

Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. (nature.com)
In 2012, Dixon 1 first proposed the concept of ferroptosis, an iron-dependent, non-apoptotic mode of cell death characterized by the accumulation of lipid reactive oxygen species (ROS). (nature.com)
The consequences for the cell can be dramatic mainly due to a reduction in the amount of ATP produced and an increase in the levels of reactive oxygen species. (bmglabtech.com)
In the present study, we have further demonstrated that HepG2 cells treated with LPS alone or in combination with aspirin induces subcellular toxic responses which are accompanied by increase in reactive oxygen species (ROS) production, oxidative stress, mitochondrial respiratory dysfunction and apoptosis. (uaeu.ac.ae)
Cell viability, reactive oxygen species (ROS) production, phagocytic function, and cytokine production were examined. (cdc.gov)
respiratory burst (the rapid release of Reactions of oxygen radicals with Mitochondrial oxidative phosphor- reactive oxygen species from cells) cel ular components can deplete an- ylation is a major source of oxy- that involves nicotinamide adenine tioxidants, can cause direct oxidative gen radicals of endogenous origin. (who.int)

Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. (nature.com)

Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. (institut-curie.org)
Here we report that the drug-like small-molecule ironomycin reduces the mitochondrial iron load, resulting in the potent disruption of mitochondrial metabolism. (institut-curie.org)
Ironomycin couples targeting of cellular metabolism with cell death by reducing mitochondrial iron, resulting in the alteration of mitochondrial metabolism and the activation of BAX/BAK. (institut-curie.org)
Progressive mitochondrial accumulation of incompletely translocated APP caused mitochondrial dysfunction and impaired cellular energy metabolism. (jneurosci.org)
Our results suggest that the altered redox metabolism, oxidative stress and mitochondrial function in HepG2 cells play a critical role in LPS/aspirin-induced cytotoxicity. (uaeu.ac.ae)
In conclusion, this study suggested that five significantly downregulated mRNAs (MAPK8, CDC42, NDUFS1, COX4I1, and SDHC) and three significantly downregulated miRNAs (miR-126-5p, miR-19-3p, and miR-29a-3p) were potentially useful diagnostic markers in clinic, and lipid metabolism (especially non-alcoholic fatty liver disease pathway) and mitochondrial dysregulation may be the keys to biochemically detectable molecular defects. (frontiersin.org)
In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.com)
In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
Furthermore, HIF-1 actively limits the mitochondrial consumption of pyruvate at two levels: (i) through the enzyme PDK (PDH-kinase), which in turn inhibits PDH activity preventing the conversion of pyruvate into acetyl CoA, and thereby limiting mitochondrial metabolism of pyruvate [ 6 ] and (ii) through the direct activation of LDH [ 7 , 8 ]. (hindawi.com)

Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. (frontiersin.org)
Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca 2+ homeostasis leading to neuroinflammation. (frontiersin.org)
Other effects include impaired cellular respiration, altered cell signaling , apoptosis , and impaired calcium homeostasis . (bmglabtech.com)
Pre-treatment of HepG2 cells with NAC exhibited a selective protection in redox homeostasis and mitochondrial dysfunction. (uaeu.ac.ae)
Ion homeostasis is crucial for mitochondrial function. (vetmeduni.ac.at)
This exchanger, which has been sought since the 1970s, is critical for maintaining mitochondrial Ca 2+ levels and pH homeostasis. (vetmeduni.ac.at)
According to the experts, further studies are now needed to understand how LETM1 and TMBIM5 link mitochondrial K + and Ca 2+ cycles and to shed more light on the regulatory mechanism of LETM1 and its interaction partners maintaining mitochondrial ion homeostasis. (vetmeduni.ac.at)

During recovery, counterregulatory mechanisms take place, and the activated cells return to the homeostatic state. (frontiersin.org)
Conversely, these mechanisms demand high energy consumption, promoting important metabolic changes in the cell. (frontiersin.org)
These adaptive molecular and structural mechanisms increase respiration to maintain basic processes specific to cell types and tissues. (nature.com)
Fig. 4: Post-translational mechanisms governing respiratory control and the role of mitochondrial membrane dynamics. (nature.com)
Although the mechanisms underlying PD remain elusive, α-Synuclein (αSyn) accumulation and mitochondrial dysfunction have been recognized as major contributors [ 1 , 57 ]. (springer.com)
How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. (nature.com)
1,2 The molecular mechanisms underlying striatal vulnerability are still unknown, but growing evidences suggest that mitochondrial dysfunction occurs during the pathogenesis of the disease. (bmj.com)
One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. (mdpi.com)
Nevertheless, the mechanisms related to the impairment of mitochondrial functions specific to AD remain unclear. (jneurosci.org)
For this program, therapeutic approaches to Alzheimer's disease (AD) and related dementias (ADRD) should have a focus on biological mechanisms related to mitochondrial/bioenergetics and inflammation. (alz.org)
Despite the pivotal role for processes downstream of beta amyloid and tau accumulations as the 'final common pathway' for dysfunction of neurons, the precise mechanisms of synapse loss in AD, dendrite pruning and/or cell death that occur in disease remain uncertain. (alz.org)
Thus, as an example (in addition to neuronal targets or other cellular types), there are opportunities to target cellular mechanisms of astrocytes, oligodendrocytes, microglia and even endothelial cells on blood vessels in order to halt, diminish and/or reverse the brain cell degeneration seen in AD or ADRD. (alz.org)
including biologic or small molecule approaches) targeting mitochondrial/bioenergetics and related biological mechanisms (i.e., inflammation response). (alz.org)
The findings of this study may enhance the current knowledge of mitochondrial-regulated cell mechanisms in breast cancer in Malaysia. (upm.edu.my)
Research in this laboratory focuses on gaining a better understanding of the mechanisms which underlie these signaling patterns with a primary goal of relating this knowledge to the physiology and pathophysiology of exocrine cells. (rochester.edu)
7 Indeed, mitochondrial dysfunction may be one of the failing compensation mechanisms that were referred to in the article. (asahq.org)
In chronic heart failure, myocardial cells die from energy starvation, from cytotoxic mechanisms leading to necrosis, or from the acceleration of apoptosis or programmed cell death. (medscape.com)
In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)

Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors. (cienciavida.org)
Hypoxia induces EMT in low and highly aggressive pancreatic tumor cells but only cancer stem-like cells acquire pronounced migratory potential. (uni-heidelberg.de)
Radiation induces caspase activation fundamentally via the mitochondrial pathway. (spandidos-publications.com)

Mitochondrial outer membrane permeabilization (MOMP), also known as the mitochondrial outer membrane permeability, is one of two ways apoptosis (programmed cell death) can be activated. (wikipedia.org)
Ironomycin promotes the recruitment and activation of BAX/BAK, but the resulting mitochondrial outer membrane permeabilization (MOMP) does not lead to potent activation of the apoptotic caspases, nor is the ensuing cell death prevented by inhibiting the previously established pathways of programmed cell death. (institut-curie.org)
Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell , leading to rapid caspase activation and apoptosis . (bvsalud.org)

Disturbances in mitochondrial dynamics may influence many cellular and molecular pathways, as calcium-dependent immune activation, transcription factors phosphorylation, cytokine secretion, organelle transference and even cell death. (frontiersin.org)
Our results suggested that flufenoxuron inhibits cell development and cell cycle progression in porcine trophectoderm (pTr) cell and porcine endometrial luminal epithelial (pLE) cell lines through the repression of signal transduction pathways. (korea.ac.kr)
ions are crucial regulators of bioenergetics and cell death pathways. (vetmeduni.ac.at)
There are multiple types of cell death, several interconnected signaling pathways can be activated, and the postmortem consequences may vary. (cshlpress.com)
Lipids, amino acids, and nucleotides necessary for the biosynthesis of the daughter cells are mostly provided by intermediate metabolites of these pathways. (hindawi.com)
To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)

Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. (bvsalud.org)
Thus, VDAC2 acts as a crucial component in mitochondrial apoptosis by allowing the mitochondrial recruitment of BAK, thereby controlling tBID-induced OMM permeabilization and cell death. (nih.gov)

Podocyte-specific deletion of Klf6 expression in mice leads to mitochondrial dysfunction and apoptosis, followed by glomerulosclerosis. (jci.org)

These mitochondrial defects can be widely rescued by Cdk5 inhibition with roscovitine or Cdk5 knockdown with siRNA transfection. (bmj.com)
Retrieved on December 11, 2023 from https://www.news-medical.net/whitepaper/20180614/Inhibition-of-Mitochondrial-Permeability-Transition-Pore-Evaluated-by-Calcium-Retention-Capacity-Assay.aspx. (news-medical.net)
ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine. (uni-heidelberg.de)
[ 8 ] Caspase inhibition in clonal striatal cells showed no correlation between the reduction of aggregates in the cells and increased survival. (medscape.com)

Traditionally, cell death has been divided into apoptosis and necrosis. (nature.com)
Recent studies have shown that in addition to necrosis and apoptosis, there are also other new programmed death modes, such as autophagy, necrosis and necrotic apoptosis, which have unique biological processes and pathophysiological characteristics. (nature.com)
It does not have the morphological characteristics of typical necrosis, such as swelling of the cytoplasm and organelles and rupture of the cell membrane, nor does it have the characteristics of traditional cell apoptosis, such as cell shrinkage, chromatin condensation, formation of apoptotic bodies and disintegration of the cytoskeleton. (nature.com)
Rupture of outer mitochondrial membrane (OMM) and ultimately cell death due to necrosis are the end results. (news-medical.net)
Disruption of mitochondrial function by drugs can result in cell death by necrosis or can signal cell death by apoptosis (e.g., following cytochrome c release). (nih.gov)
Necrosis stimulates fibroblast proliferation, which results in the replacement of myocardial cells with collagen. (medscape.com)
The extrinsic pathway is triggered by binding of death ligands, such as tumor necrosis factor (TNF)-α, to death receptors of the TNF family, which results in the assembly of a receptor-associated complex. (spandidos-publications.com)

The reason is because many immune-related receptors and molecules are extensively produced by these cells, not only during disease but also during physiological processes ( 3 , 9 ). (frontiersin.org)
These powerhouses of the cell generate most of the energy needed to drive essential biological reactions and processes. (bmglabtech.com)
This research is highly significant as it will stimulate the field to consider and investigate connections between individual mitochondrial processes, such as cell death and mitophagy. (elsevierpure.com)
AIMS: To review the role played by the mitochondrial permeability transition pore (MPTP) in different physiological and pathological processes. (lu.se)
The mitochondrion seems to play an important part in the cellular decision making that leads, irreversibly, toward the execution phase in cellular death processes. (lu.se)

Many factors can contribute to mitochondrial dysfunction including genetic mutations, aging, environmental factors, nutritional deficiencies, and metabolic disorders. (bmglabtech.com)
However, a drug that directly couples targeting of a metabolic dependency with the induction of cell death in cancer cells has largely remained elusive. (institut-curie.org)
Since metabolic suppression was suggested to mitigate DNA damage ( Koubova & Guarente, 2005 ), a novel model deciphering CR-conferred DNA protection has been established, in which CR-mediated metabolic/hormonal adaptations result in cellular adaptations including reduced cell proliferation, increased autophagy or apoptosis, up-regulated DNA repair systems, and enhanced genomic stability ( Longo & Fontana, 2010 ). (peerj.com)
Metabolic adaptations of cancer cells. (hindawi.com)
This buildup of lactic acid may help distinguish a mitochondrial disorder from other metabolic diseases. (msdmanuals.com)

In addition, mutations in mitochondrial DNA have been associated with an increased risk of the disease. (bmglabtech.com)
We explored the use of naturally occurring somatic mutations in mitochondrial transcripts detected in single-cell RNA-seq as genetic lineage barcodes in HPSC. (biorxiv.org)

During MOMP, it takes about five minutes for all mitochondrial membranes within a cell to permeabilize. (wikipedia.org)
Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. (nih.gov)
This being the case, the action would be mediated by the permeability of its membranes, through the formation of the mitochondrial permeability transition pore, and would involve phenomena such as the dissipation of the mitochondrial electrochemical potential and the release of substances from within it. (lu.se)

It is important to test for mitochondrial toxicity early in drug development as impairment of mitochondrial function can induce various pathological conditions that are life threatening or can increase the progression of existing mitochondrial diseases. (nih.gov)

It is part of the intrinsic pathway of apoptosis, also known as the mitochondrial pathway. (wikipedia.org)
Although all Ca2+ mobilizing agonists in pancreatic acinar cells utilize the phosphoinositide-signaling (PI) pathway, stimulation by individual agents results in markedly different temporal and spatial patterns of Ca2+ signaling. (rochester.edu)
The central element in the mitochondrial pathway is a specialised protein complex, the apoptosome, which enables and facilitates the activation of procaspase 9. (spandidos-publications.com)
Radiation and other agents induce caspase activation fundamentally via the mitochondrial pathway, which includes mitochondrial integration of apoptotic signals and the subsequent release of cytochrome c into the cytosol ( 5 , 9 , 10 ). (spandidos-publications.com)

These mitochondrial dynamics, they report, are dependent on caspases, the Bcl-2 family, the mitochondrial fission and fusion machinery and the autophagic machinery. (biologists.com)

On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. (frontiersin.org)
Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease. (frontiersin.org)
Recent research has revealed important correlation of mitochondrial dynamics and the pathophysiology of brain diseases, as Alzheimer's. (frontiersin.org)
Some deregulatory miRNAs were detected in the humans that lead to mitochondrial dysfunction, altered mitochondrial dynamics, oxidative stress, excitotoxicity, and the accumulation of SNCA, consequently resulting in neurodegeneration ( Martin, 2010 ). (frontiersin.org)

4 Cellular P o 2 is kept in narrow range under normal conditions as either hypoxia or hyperoxia can result in mitochondrial dysfunction. (asahq.org)
Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)

These potent effects are driven by curcumin's ability to induce G2/M cell cycle arrest, induce autophagy, activate apoptosis, disrupt molecular signaling, inhibit invasion and metastasis, and increase the efficacy of current chemotherapeutics. (wellnessresources.com)
Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells. (uni-heidelberg.de)

Mitochondrial DNA (mtDNA) mutations, oxidative stress and resistance to cell deaths increase one's risk for breast cancer. (upm.edu.my)
Mitochondrial diseases are caused by mutations to mitochondrial DNA (mtDNA) gene or a mutation in a nuclear gene (nDNA). (mdlinx.com)
There are many kinds of mitochondrial diseases, and more than 250 pathogenic mutations to mtDNA have been reported. (mdlinx.com)

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. (nature.com)
Both α-Synuclein (αSyn) accumulation and mitochondrial dysfunction have been implicated in the pathology of Parkinson's disease (PD). (springer.com)
Overexpression of ClpP reduces αSyn-induced mitochondrial oxidative stress through enhancing the level of Superoxide Dismutase-2 (SOD2), and suppresses the accumulation of αSyn S129 phosphorylation and promotes neuronal morphology in neurons derived from PD patient iPS cells carrying αSyn A53T mutant. (springer.com)
Mitochondrial accumulation of APP was also observed in the cholinergic, dopaminergic, GABAergic, and glutamatergic neuronal types in the category III AD brains. (jneurosci.org)
Collectively, these results suggest that abnormal accumulation of APP across mitochondrial import channels, causing mitochondrial dysfunction, is a hallmark of human AD pathology. (jneurosci.org)
Fatty liver is the accumulation of triglycerides and other fats in the liver cells. (medscape.com)
Its unique signature that distinguishes it from other forms of cell death is the formation and accumulation of lipid hydroperoxides, particularly oxidized forms of polyunsaturated phosphatidylethanolamines (PEs), which drives cell death. (cdc.gov)

In this application, we propose experiments that bi-directionally connect Bax, a central mediator of cardiomyocyte death, with Parkin, an important activator of mitophagy in cardiomyocytes. (elsevierpure.com)
Using genetic manipulations, we have found unexpectedly that endogenous levels of Bax in healthy cells suppress mitophagy. (elsevierpure.com)
Accordingly, the over-arching hypothesis of this project is that Bax and Parkin antagonize each other for the benefit of cardiomyocytes: The binding of Bax, likely in its cell death-inactive conformation, to Parkin inhibits Parkin-mediated mitophagy to prevent mitochondrial depletion. (elsevierpure.com)
This is an MPI application that brings together the expertise of Richard Kitsis (cardiomyocyte death) and Gerald Dorn (cardiac mitophagy). (elsevierpure.com)
Curcumin causes cell death and primarily initiates an autophagic step (mitophagy). (wellnessresources.com)

Their paper is titled "The Parksinonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine-producing axons. (genengnews.com)

A drastic rise in permeability of inner mitochondrial membrane (IMM), through consistent opening of a multi-protein channel referred to as the mitochondrial permeability transition pore (MPTP) results in mitochondrial dysfunction. (news-medical.net)
We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). (mdpi.com)

Frequently, low doses of natural chemical products activate an adaptive stress response, whereas high doses activate acute responses like autophagy and cell death. (wellnessresources.com)
Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment. (uni-heidelberg.de)

Scientists find that respiratory organelles in toxin-treated cells stop circulating along neuronal axon. (genengnews.com)
4 Interestingly, Cdk5 has been shown to act as a mitochondrial regulator during neuronal apoptosis. (bmj.com)
Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. (bmj.com)
Neuronal cell apoptosis is associated with various neurological damaging factors, including radiation ( 1 ). (spandidos-publications.com)
Studies on the molecular mechanism of neuronal cell apoptosis following radiation have enriched the number of protective therapeutic strategies against radiation-induced neuronal cell death ( 2 ). (spandidos-publications.com)
[ 7 ] More recent data from striatal neuronal cultures transfected with mutant huntingtin and transgenic mice carrying the spinocerebellar ataxia-1 (SCA-1) gene (another CAG repeat disorder) suggest that NIIs may not be necessary or sufficient to cause neuronal cell death, but translocation into the nucleus is sufficient to cause neuronal cell death. (medscape.com)

Mutations that cause mitochondrial complex I deficiency impair the formation or function of complex I. As a result, complex I activity is reduced and oxidative phosphorylation is impaired. (medlineplus.gov)
Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)

During apoptosis , the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases . (bvsalud.org)

The pathogenesis of ischemia-reperfusion injury of heart, acute pancreatitis, neurodegeneration and brain and kidney, muscular dystrophies, have a common key characteristic - mitochondrial abnormality. (news-medical.net)

Evidence also points to multiple genes being linked to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
In Parkinson's disease, a strong link between mitochondrial dysfunction and disease-associated genes has been documented. (bmglabtech.com)
Mutations in many genes can cause mitochondrial complex I deficiency. (medlineplus.gov)
Most genes known to be involved in mitochondrial complex I deficiency are found in nuclear DNA, which is packaged in chromosomes within the cell nucleus . (medlineplus.gov)
This is the first demonstration that defective transcriptional regulation of nuclear-encoded mitochondrial genes can result in experimental glomerular disease. (jci.org)
Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
Genes Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or the code for functional ribonucleic. (msdmanuals.com)

We first observed that striatal cells expressing mutant huntingtin (mHtt) present increased mitochondrial fragmentation that worsens after dopaminergic stimuli. (bmj.com)
Flufenoxuron induced programmed cell death through DNA fragmentation and apoptotic signals. (korea.ac.kr)

The World Health Organization (WHO) have estimated that until 2030, deaths attributed to neurological diseases will increased up to 12.22% ( 1 ). (frontiersin.org)
A common feature of neurodegenerative and neuroinflammatory diseases is the activation of CNS resident cells ( 2 - 4 ). (frontiersin.org)
The disruption of mitochondrial function is known to be linked to neurodegenerative diseases. (bmglabtech.com)
Find out how microplate readers advance research into mitochondrial dysfunction and different neurodegenerative diseases. (bmglabtech.com)
The disruption of mitochondrial function is a known contributor to neurodegenerative diseases like Parkinson's and Alzheimer's disease, although the precise details remain to be worked out. (bmglabtech.com)
Mitochondrial diseases are thought to occur in about 1 in 8,500 people. (medlineplus.gov)
Identifying therapies that target mitochondrial/ bioenergetics and inflammation may have the potential to treat complex underlying biology of AD and ADRD, while also gaining a deeper understanding of multiple diseases that affect the brain. (alz.org)
Mitochondrial diseases are complex, currently incurable, and can be life-threatening. (mdlinx.com)
There are multiple types of mitochondrial diseases. (mdlinx.com)
Dr. Ganesh says mitochondrial diseases are genetically inherited. (mdlinx.com)

Here, we show that the protein level of ClpP is selectively decreased in αSyn-expressing cell culture and neurons derived from iPS cells of PD patient carrying αSyn A53T mutant, and in dopaminergic (DA) neurons of αSyn A53T mice and PD patient postmortem brains. (springer.com)
Compensating for the loss of ClpP in the substantia nigra of αSyn A53T mice by viral expression of ClpP suppresses mitochondrial oxidative damage, and reduces αSyn pathology and behavioral deficits of mice. (springer.com)
Hepatocyte death by apoptosis occurs in alcoholic fatty liver and has been demonstrated in rats and mice after ethanol feeding. (medscape.com)
By testing three different cell types, with two being from humans and one from mice, with different levels of exposure to UV rays. (yourtango.com)

Caspases are synthesized in the cell as inactive zymogens and require to be activated to be functional. (spandidos-publications.com)
z-VAD-fmk ( N -benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) is a powerful, irreversible and cell permeable inhibitor of caspases, and has been demonstrated to directly block the activity of caspases ( 13 ). (spandidos-publications.com)

Enrichment of c-Met+ tumorigenic stromal cells of giant cell tumor of bone and targeting by cabozantinib. (uni-heidelberg.de)
Rescue of silenced UCHL1 and IGFBP4 expression suppresses clonogenicity of giant cell tumor- derived stromal cells. (uni-heidelberg.de)
Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
Typically, rapidly proliferating tumor cells have glycolytic rates up to 200 times higher than those of their normal tissue of origin, even in the presence of oxygen [ 3 ]. (hindawi.com)

ATP-dependent Clp protease (ClpP), a mitochondrial matrix protease, plays an important role in regulating mitochondrial protein turnover and bioenergetics activity. (springer.com)
Part the Cloud will promote human studies to advance innovative ideas for early phase human trials (Phase 1 or Phase 2) that address therapies (an experimental or repurposed drug) to address mitochondrial/ bioenergetics and inflammation. (alz.org)

At higher doses, cells undergo mitochondrial destabilization due to calcium release from the endoplasmic reticulum, and die. (wellnessresources.com)

Predicted to be involved in protein import into mitochondrial matrix. (nih.gov)

We modeled the development of embryonic tissues from hPSCs and delineated the ontogeny of hematopoietic cells by mitochondrial variant lineage tracing. (biorxiv.org)

Researchers believe that problems with oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. (medlineplus.gov)

Interestingly, mitochondrial translocation of APP was incomplete because of an internal acidic domain present between 220 and 290 amino acids. (jneurosci.org)

Altogether, our findings support the hypothesis that Cdk5 plays a crucial role in mitochondrial defects involved in the striatal neurodegeneration in HD. (bmj.com)

Mitochondrial complex I deficiency is a shortage (deficiency) of a protein complex called complex I or a loss of its function. (medlineplus.gov)
Mitochondrial complex I deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). (medlineplus.gov)
People with mitochondrial complex I deficiency typically have neurological problems, such as abnormal brain function (encephalopathy), recurrent seizures (epilepsy), intellectual disability, difficulty coordinating movements (ataxia), or involuntary movements (dystonia). (medlineplus.gov)
People with mitochondrial complex I deficiency sometimes have heart, liver, or kidney problems. (medlineplus.gov)
Some people with mitochondrial complex I deficiency have groups of signs and symptoms that are classified as a specific syndrome. (medlineplus.gov)
For example, a condition called Leigh syndrome is most commonly caused by mitochondrial complex I deficiency. (medlineplus.gov)
Another condition that can be caused by mitochondrial complex I deficiency, Leber hereditary optic neuropathy , is associated mainly with vision problems due to optic nerve degeneration. (medlineplus.gov)
Mitochondrial complex I deficiency is the most common cause of mitochondrial disease in children, accounting for approximately 30 percent of cases. (medlineplus.gov)
Mitochondrial complex I deficiency has several inheritance patterns, depending on the gene involved. (medlineplus.gov)

They carry out aerobic respiration, a process that involves the breakdown of glucose and other fuel molecules to produce ATP through a series of interconnected reactions, including the citric acid cycle and the mitochondrial electron transport chain. (bmglabtech.com)

Fig. 3: Translational control of mitochondrial respiratory chain assembly. (nature.com)

consequently, the cytosolic and mitochondrial calcium levels were increased. (korea.ac.kr)
In exocrine acinar cells regulation of intracellular calcium plays a pivotal role in controlling fluid and protein secretion. (rochester.edu)
Exposure of cells to neurotransmitters and hormones results in a rapid elevation of intracellular calcium. (rochester.edu)
A further project relates to the organization and regulation of calcium release sites in exocrine cells. (rochester.edu)
Cell calcium. (rochester.edu)

The role of mitochondrial Ca 2+ buffering has been extensively studied, yet some of the players in maintaining Ca 2+ balance have not been identified. (vetmeduni.ac.at)
Sulforaphane decreases kidney injury after transplantation in rats: role of mitochondrial damage. (uni-heidelberg.de)

Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. (medscape.com)

MOMP has been referred to as the point of no return for apoptosis, almost always resulting in the completion of the process, and thus, cell death. (wikipedia.org)
Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death . (bvsalud.org)

The Lily Foundation, the UK's leading mitochondrial disease charity, says that a "substantial number of children with mitochondrial disorders do not reach adulthood. (mdlinx.com)

Cytosolic and mitochondrial forms the cancer phenotype. (who.int)

Cell Death & Differentiation. (wikipedia.org)
The ability to perform lineage tracing at the single-cell level is critical to reconstructing dynamic transitions during cell differentiation. (biorxiv.org)
KLF family members are expressed in most if not all tissues and have diverse roles in organismal development and cell differentiation, function, and death. (jci.org)

Hence, for the prevention of cell death in a variety of disease conditions, the MPTP is a potential target. (news-medical.net)

Substantial evidence has shown that αSyn toxicity may directly disrupt mitochondrial function. (springer.com)
According to the first authors of the study, Shane Austin, Ronald Mekis and Sami Mohammed from the Department of Physiology and Biophysics at Vetmeduni, "Biochemical assays in human cells demonstrate that TMBIM5 is essential for the H + -dependent mitochondrial Ca 2+ release and that a mutation in the pH-sensing domain of TMBIM5 completely or severely reduces this function. (vetmeduni.ac.at)
Finally, there is a cell-to-cell variability in mitochondrial number and function. (asahq.org)
Nitric oxide and glucocorticoids synergize in inducing apoptosis of CD4+8+ thymocytes: Implications for "Death by Neglect" and T cell function. (uni-heidelberg.de)
This may lead to cell injury or even cell death and body systems will not function properly. (msdmanuals.com)

Genetic and structural characterization of the human mitochondrial inner membrane translocase. (nih.gov)
In this study, we used an enrichment of scRNA-seq mitochondrial reads and a robust computational method to identify clonally relevant mitochondrial variants as endogenous genetic barcodes for clonal tracking of early embryonic hematopoiesis from hPSC. (biorxiv.org)
The glomerular podocyte is particularly sensitive to mitochondrial dysfunction, as seen in various genetic disorders manifesting as progressive glomerulosclerosis. (jci.org)

The researchers show that, during this event, the mitochondrial networks of ovarian nurse cells undergo extensive remodelling, cluster formation and cluster engulfment by somatic follicle cells. (biologists.com)

These mitochondrial responses are governed by general principles of regulatory biology exemplified by changes in gene expression, protein translation, protein complex formation, transmembrane transport, enzymatic activities and metabolite levels. (nature.com)
Keep up with the Node 'Lab meeting' posts as the platform regularly highlights development and stem cell biology labs from across the globe and showcases research and researchers from the community. (biologists.com)

Thirumalesh's case echoes that of an infant named Charlie Gard, who died from encephalomyopathic mitochondrial DNA depletion syndrome (MDDS). (mdlinx.com)

Anatomy6

Organisms2

Diseases5

Chemicals and Drugs25

Analytical, Diagnostic and Therapeutic Techniques and Equipment6

Psychiatry and Psychology1

Phenomena and Processes17

Information Science1

Health Care2

Mitochondria30

Proteins22

Associated with mitochondrial dysfunction2

Altering mitochondrial dynamics1

Biogenesis6

Reactive oxygen6

Uncoupling protein1

Metabolism9

Homeostasis7

Mechanisms18

Induces3

Outer membrane permeabilization3

Pathways6

Permeabilization2

Dysfunction and apoptosis1

Inhibition5

Necrosis7

Processes5

Metabolic5

Mutations in mitochondrial2

Membranes3

Impairment of mitochondrial1

Pathway4

Fission and fusion1

Dynamics4

Cellular3

Induce2

MtDNA3

Accumulation7

Mitophagy5

Impairs mitochondrial1

Permeability Transition2

Autophagy2

Neuronal6

Impair2

Cytochrome1

Abnormality1

Genes7

Fragmentation2

Diseases10

Mice4

Caspases2

Tumor5

Bioenergetics2

Endoplasmic reticulum1

Protein import1

Hematopoietic cells1

Oxidative phosphorylation1

Translocation1

Neurodegeneration1

Deficiency9

Electron trans1

Respiratory chain1

Calcium5

Role2

Neurons1

MOMP2

Adulthood1

Cytosolic1

Differentiation3

MPTP1

Function5

Genetic3

Somatic1

Biology2

Depletion1