Extrinsic and intrinsic mitochondrial pathways. Medical search. Frequent questions

In intrinsic activation, cytochrome c from the mitochondria works in combination with caspase-9, apoptosis-activating factor 1 (Apaf-1), and ATP to process procaspase-3. (wikipedia.org)
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)
Breaching the mitochondrial OM releases apoptogenic factors, including cytochrome c and DIABLO (also known as Smac), which activate a group of aspartate-specific proteases known as caspases ( Youle and Strasser, 2008 ). (biologists.com)
BCL2 proteins are described as 'crucial regulators of apoptosis' (PMID:15868100)and the intrinsic apoptosis pathway is initiated by the release of mitochondrial cytochrome c into the cytoplasm, which results in the activation of caspases (15102863) - help in generating a defintion for intrinsic apoptosis? (geneontology.org)
The intrinsic apoptotic pathway is characterized by permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm. (geneontology.org)
mitochondrial membrane permeability → cytochrome c & AIF → activates caspases → death. (howmed.net)
The central event in the 'intrinsic' pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. (kegg.jp)

There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. (spandidos-publications.com)
The extrinsic pathway is associated with membrane receptors and their ligands, and the intrinsic pathway is dependent on mitochondria ( 5 ). (spandidos-publications.com)
Within the cell, TSPO is predominantly located in mitochondria, specifically in the outer mitochondrial membrane. (uni-regensburg.de)
and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins ( Fig. 1 ). (biologists.com)
By contrast, the extrinsic apoptotic pathway can activate caspases without the participation of mitochondria. (biologists.com)
Mitochondria could be targeted in the development of novel antidepressant drugs, and specific forms of mitochondrial dysfunction could be identified as biomarkers to personalize treatment and aid in early diagnosis by differentiating between disorders with overlapping symptoms. (frontiersin.org)
induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. (1library.net)
With regard to the intrinsic apoptosis pathway, HSP70 can bind directly to the pro-apoptotic BCL2 family member BAX and prevent it from translocating to mitochondria, where the latter disrupts mitochondrial membranes following an apoptotic stimulus. (biomedcentral.com)

The caspases can be activated through either the intrinsic (mitochondrial mediated) or extrinsic (death receptor mediated) apoptotic pathways. (geneontology.org)

These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. (kegg.jp)

It may be activated via death receptors (extrinsic pathway) or mitochondrial (intrinsic pathway). (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)
Methods: To assess extrinsic pathways, we measured hepatic expression of death-inducing cytokine receptors (tumor necrosis factor-α-receptor (TNF-R)1, TNF-R2, Fas, and TNFα-related apoptosis-inducing ligand-receptor (TRAIL-R) mRNA, TUNEL, caspase 3 activation, liver injury and liver pathology in mice fed a methionine and choline deficient (MCD) diet. (edu.au)
The 'extrinsic' pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. (kegg.jp)
Extracellular signals activating death receptors triggers the extrinsic pathway, and intracellular stress activates the intrinsic pathway. (cancer-research-network.com)
Molecular chaperones are essential for stabilizing the fragile structures of many receptors, protein kinases, and transcription factors that participate in the pathways of normal cellular growth. (biomedcentral.com)

Autophagy is an intracellular catabolic pathway in which cellular constituents are engulfed by autophagosomes and degraded upon autophagosome fusion with lysosomes. (nature.com)
Intracellular insults can initiate neuronal apoptosis via mitochondrial dysfunction or intrinsic pathway (Fig. 1 ). (biomedcentral.com)
Characterization Eumycetoma of the result of INA 6 cells to JAK inhibition revealed effects on intracellular signaling pathways, growth, and apoptosis, each occurring within the same relative concentration array of INCB16562. (igfprotein.com)

IL-21 activates both the Raf-ERK-MAPK and the Jak/STAT signaling pathways. (intechopen.com)

Midazolam induces apoptosis via activation of the mitochondrial pathway in a concentration-dependent manner. (bmj.com)

Autophagy is generally considered as a cell survival/protection mechanism because it removes toxic or obsolete proteins and organelles and recycles the degradation products for use as sources for energy and metabolites in anabolic pathways 3 . (nature.com)
Label-free quantitative proteomic analyses using liquid chromatography in conjunction with a tandem mass spectrometry (LC-MS/MS) system showed significant alteration of mitochondrial, cytosolic, nuclear and cytoskeletal proteins in fetal brains exposed prenatally to alcohol [ 17 ]. (biomedcentral.com)
The intrinsic apoptotic pathway is initiated in response to a variety of stress signals ( Willis and Adams, 2005 ), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage ( Fig. 1 ). (biologists.com)
In this review, we summarize some of the latest knowledge on mitochondrial dysregulation in major depression (depicted in Figure 1 ) and also discuss how mitochondrial dysfunction could instigate downstream changes in extracellular matrix proteins such as reelin, neuronal nitric oxide (nNOS), oxidative stress, and inflammation, and finally adult hippocampal neurogenesis. (frontiersin.org)
Anti-apoptotic strategies include inhibition of caspase, poly [ADP-ribose] polymerase (PARP), and Bcl-2 proteins as well as induction of the PKB/Akt pathway and inhibitors of apoptosis (IAP) family of proteins. (biomedcentral.com)
It largely regulated at the mitochondrial outer membrane (MOM) by the pro- and anti-apoptotic members of the B cell lymphoma 2 (Bcl-2) family of proteins. (cancer-research-network.com)
In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. (typeset.io)
But recent evidence suggests that these two skin ageing processes have common biochemical and molecular pathways, including nuclear and mitochondrial DNA damage, inactivation of growth factors, breakdown of matrix proteins and membrane lipid damage. (okdermo.com)
How do distinct transcriptional regulatory proteins coordinate their job with extrinsic factors and the microenvironment? (nih.gov)

Mitochondrial outer membrane permeabilisation (MOMP) is the point of no return in many forms of apoptotic cell death. (biologists.com)
The current development of anti-cancer agents that target the Bcl-2 protein family is showing considerable promise, although how this targeting triggers Bak and Bax to perform their crucial function of mitochondrial outer membrane permeabilisation (MOMP) is not clear. (biologists.com)
MSN-125 prevents mitochondrial outer membrane permeabilization. (cancer-research-network.com)

Nutritional restitution experiments showed that correcting either methionine or choline deficiency suppressed liver inflammation (extrinsic pathway), but failed to correct apoptosis, IGF-1 or p53. (edu.au)

In this paper, we make the case that mitochondrial dysfunction could play an important role in the pathophysiology of depression. (frontiersin.org)
However, the data in relation to antidepressant drug effects are contradictory: some studies reveal they have no effect on mitochondrial function or even potentiate dysfunction, whereas other studies show more beneficial effects. (frontiersin.org)
The focus of this review is the link between mitochondrial dysfunction and major depression. (frontiersin.org)

Apoptosis induced by tungsten carbide-cobalt nanoparticle s in JB6 cells involves ROS generation through both extrinsic and intrinsic apoptosis pathways. (cdc.gov)
Apoptosis induced by WC-Co nanoparticle s and fine particles involves both extrinsic and intrinsic apoptosis pathways. (cdc.gov)
The mechanism of apoptosis is complex and involves many pathways. (biomedcentral.com)

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)
TSPO is a ubiquitous mitochondrial protein and is involved in numerous biological functions. (uni-regensburg.de)
In addition to its role in glucose metabolism, this pathway also regulates the redirection of free amino acids to protein synthesis via the mTOR-signaling pathway. (hindawi.com)
However, in certain cell types, the extrinsic pathway also induces mitochondrial damage by cleaving the pro-apoptotic Bcl-2 family protein Bid to its activated truncated form (tBid), which leads to Bak and Bax activation. (biologists.com)
B-cell lymphoma (Bcl2) protein overexpressing and caspase 9-deficient lymphoma cells were used to determine the role of the mitochondrial (intrinsic) pathway. (bmj.com)
Caspase 8-deficient and Fas-associated protein with death domain (FADD)-deficient cells were used to evaluate the death receptor (extrinsic) pathway. (bmj.com)
The results of the present study suggest that P. vivax infection induces apoptosis of CD4 + T cells mediated by two types of signaling: by activation of the TNFR1 death receptor (extrinsic pathway), which is amplified by Bid, and by decreased expression of the anti-apoptotic protein Bcl-2 (intrinsic pathway). (biomedcentral.com)

Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
Apoptosis is most often mediated by extrinsic pathway via FAS or CD95 or apoptosis antigen 1 (APO-1) or tumor necrosis factor receptor superfamily 6 (TNFRSF6), a cell surface death receptor. (medscape.com)
Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. (bvsalud.org)
Using genetic manipulation of cell death pathways, we found the monocytic suppressor- cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8 -dependent, RIPK3-independent cell death . (bvsalud.org)
Development of the granulocyte subset requires MCL-1-mediated control of the intrinsic mitochondrial death pathway. (bvsalud.org)
Thus, death pathway modulation defines the development, survival , and function of myeloid suppressor cells . (bvsalud.org)
Cell death occurs under physiological and pathological conditions and mediates through three pathways as follows: apoptosis, autophagic cell death, and necrosis. (biomedcentral.com)
The p53 induced by nutritional stress is biologically active in mediating mitochondrial cell death pathways, but may also be responsible for TRAIL receptor expression, thereby linking intrinsic and exogenous apoptosis pathways in NASH. (edu.au)
Active cell death (apoptosis, necroptosis, pyroptosis ferroptosis, alkaliptosis and oxeiptosis) are tightly regulated by signaling pathways. (nutritionfit.org)
The major signaling pathways triggering apoptotic cell death are the mitochondrial (the intrinsic) pathway and the death receptor (the extrinsic) pathway. (nutritionfit.org)
Previously, necrosis was considered an uncontrolled form of death occurring as a consequence of infection or injury, but it is now recognized that at least one pathway of active necrosis exists. (nutritionfit.org)
Overexpression of HSP70 can provide a selective survival advantage to tumor cells in part due to its ability to inhibit multiple pathways of cell death, including both intrinsic and extrinsic apoptosis. (biomedcentral.com)
Necroptosis is often compared to apoptosis, another programmed cell death pathway. (bioradiations.com)
The two cell death pathways share several upstream signaling elements and eventually lead to plasma membrane rupture, but the cell morphologies of each process are drastically different. (bioradiations.com)
the intrinsic/mitochondrial apoptotic program is implicated by the data as the main effector pathway in the observed cell death. (igfprotein.com)
Can we find common cellular pathways associated with photoreceptor cell death caused by distinct genetic mutations? (nih.gov)

In addition, as the intrinsic apoptotic pathway seems to have evolved at the same time as multicellular organisms, whereas the extrinsic pathway is a more recent evolutionary development in veterbrates, it is felt the intrinsic mechanism was more suited to a multi-organism curation project. (geneontology.org)

We hypothesized that FO might regulate related genes in apoptosis and PI3K-AKT pathways to mediate the proliferation and apoptosis of liver cancer cells. (hindawi.com)

This extrinsic activation then triggers the hallmark caspase cascade characteristic of the apoptotic pathway, in which caspase-3 plays a dominant role. (wikipedia.org)

Most cases of ALPS are caused by loss-of-function mutations in components of the FAS apoptotic pathway or extrinsic pathway. (medscape.com)
In general these mutations produce an increase in signaling pathways downstream of JAK2. (biomedcentral.com)

VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. (researchsquare.com)

Indeed, OEO/thymol increased the Reactive Oxygen Species (ROS) level leading to mitochondrial membrane potential (MMP, ΔΨm) loss, caspase-3 activation and DNA damage caused S-phase cell cycle arrest. (irost.org)
These include changes affecting mitochondrial DNA, membrane permeability, and increased formation of reactive oxygen species (ROS). (frontiersin.org)

Alterations in mitochondrial functions such as oxidative phosphorylation (OXPHOS) and membrane polarity, which increase oxidative stress and apoptosis, may precede the development of depressive symptoms. (frontiersin.org)
Functional pathway enrichment analysis by Ingenuity Pathway Analysis (IPA) revealed that the most enriched signaling pathways in aged mice lungs are involved in the regulation of cell apoptosis, senescence, development, oxidative stress, and inflammation. (aging-us.com)

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). (typeset.io)

ALPS is rarely caused by a defect of mitochondrial apoptosis or intrinsic pathway. (medscape.com)
An NRAS mutation has been identified that represents the first identified case of ALPS resulting from a defect in the intrinsic, or mitochondrial, apoptotic pathway. (medscape.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)

Interestingly, antidepressant medication can restore the mitochondrial oxidant/antioxidant balance, and therefore help to rescue the negative effects of mitochondrial dysregulation (green lines). (frontiersin.org)

The brain is particularly dependent on mitochondrial activity due to both its high levels of energy use and its inability to store large amounts of energy reserves in the form of glycogen. (frontiersin.org)

HSP70 reduces caspase activation (mainly caspase-3) and suppresses mitochondrial damage and nuclear fragmentation. (biomedcentral.com)

Organ failure in the heart or kidney can initiate various complex metabolic, cell-mediated and humoral pathways affecting distant organs, contributing to the high therapeutic costs and significantly higher morbidity and mortality. (biomedcentral.com)

Aging of the skin is mediated by a combination of the effects of time (intrinsic aging) and environmental factors (extrinsic ageing) on skin cells and their extracellular support matrix. (okdermo.com)

These pathways mediate some of the effects of IL-21. (intechopen.com)

Calyeca J , Balderas-Martínez YI , Selman M , Pardo A , . Transcriptomic profile of the mice aging lung is associated with inflammation and apoptosis as important pathways. (aging-us.com)
Using the miRNet database we identified TNFα, mTOR, TGFβ, WNT, FoxO, Apoptosis, Cell cycle, and p53 signaling pathways as the potential targets of several of the dysregulated miRNAs supporting that old lungs have increased susceptibility for apoptosis, inflammation, and fibrosis. (aging-us.com)

The study aims to evaluate the apoptotic pathway and to investigate the protective effects of the benzodiazepine antagonist flumazenil and the caspase inhibitor N -(2-quinolyl)valyl-aspartyl-(2,6-difluorophenoxy)-methylketone. (bmj.com)
Background and Aims: We examined extrinsic and intrinsic (endogenous) mitochondrial apoptosis pathways in experimental non-alcoholic steatohepatitis (NASH). (edu.au)

They are executed through different, but sometimes overlapping, signaling pathways in response to specific stimuli. (nutritionfit.org)
The 'intrinsic' pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. (kegg.jp)

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)

The induction of apoptosis and necrosis by midazolam is presumably unrelated to GABA A receptor pathway signaling. (bmj.com)

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)

As detailed in the right side of the image, there are a series of mitochondrial alterations that have been observed both in depressed patients and in animal models of depression (red lines). (frontiersin.org)

In this chapter, we will focus on IL-21's biological effects and signaling pathways as well as discuss the potential implications and applications of IL-21 in leukemia cells. (intechopen.com)
In the present study, the occurrence of apoptosis and its pathways in CD4 + T cells was investigated in naturally Plasmodium vivax -infected individuals from a Brazilian endemic area (Porto Velho - RO). (biomedcentral.com)
Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. (biomedcentral.com)
We are now focused on delineating the transcription factors and signaling pathways that are responsible for generating photoreceptors from retinal progenitor cells. (nih.gov)

The third major pathway is initiated by the constituents of cytotoxic granules (e.g. (kegg.jp)

This article gives a comprehensive review of apoptosis, its mechanisms, how defects along the apoptotic pathway contribute to carcinogenesis and how apoptosis can be used as a vehicle of targeted treatment in cancer. (biomedcentral.com)
This review discusses the recent findings regarding sarcopenia, the intrinsic, and extrinsic mechanisms involved in the onset and progression of this disease and the treatment approaches that have been developed based on testosterone deficiency and their implications. (frontiersin.org)
What are intrinsic control mechanisms that lead to photoreceptor cell fate from retinal progenitors? (nih.gov)
Environmental factors that can detect specific IgE antibodies against most low-molecular- affect the initiation of occupational asthma include the intrinsic weight agents has resulted in a search for alternative or characteristics of causative agents as well as the influence of the complementary physiopathologic mechanisms leading to airway level and route of exposure at the workplace. (cdc.gov)

Indeed, most of the intrinsic as well as extrinsic (systemic) muscle changes that occur with age are believed to be involved in the development of sarcopenia ( 5 , 6 ). (frontiersin.org)

[ 2 ] Other ALPS-associated genetic defects in the apoptotic pathway and ALPS-like disorders (ALPS-related syndromes) have subsequently been identified. (medscape.com)

Anatomy8

Organisms4

Chemicals and Drugs44

Analytical, Diagnostic and Therapeutic Techniques and Equipment4

Phenomena and Processes12

Cytochrome7

Mitochondria8

Apoptotic pathways1

Caspases1

Receptors6

Intracellular3

Activates1

Apoptosis via1

Proteins9

Outer3

Failed to correct a1

Dysfunction3

Involves3

Protein7

Death16

Mechanism1

PI3K-AKT1

Caspase cascade1

Mutations2

Downstream1

Reactive Oxygen2

Oxidative2

Autophagy1

Defect2

Metabolites1

Tightly regulated1

Dysregulation1

Dependent1

Nuclear1

Initiate1

Extracellular1

Mediate1

Inflammation2

Aims2

Stimuli2

Inhibits1

Necrosis1

Metabolism1

Alterations1

Cells4

Constituents1

Mechanisms4

Occur1

Genetic1