ArticleMolecular and cellular biology2007
Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Identification of abnormal nuclear and mitochondrial genes in esophageal cancer cells.Molecular medicine reports · 2018Article
- Autophagic cell death participates in POMC-induced melanoma suppression.Cell death discovery · 2018Article
- [Effect of hypoxia on the biological characteristics of human dental follicle cells].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2017Article
- Bcl-2 family member Mcl-1 expression is reduced under hypoxia by the E3 ligase FBW7 contributing to BNIP3 induced cell death in glioma cells.Cancer biology & therapy · 2016Article
- Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities.Cell reports · 2016Article
- The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos.Disease models & mechanisms · 2013Article
- Metabolic stress in autophagy and cell death pathways.Cold Spring Harbor perspectives in biology · 2012Review
- The novel Bcl-2 inhibitor ABT-737 is more effective in hypoxia and is able to reverse hypoxia-induced drug resistance in neuroblastoma cells.Molecular cancer therapeutics · 2011Article
- Cell metabolism: an essential link between cell growth and apoptosis.Biochimica et biophysica acta · 2011Review
- Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1.The Journal of clinical investigation · 2011Article
- Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis.PloS one · 2011Article
- Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.BMC cancer · 2010Article
- The metabolic life and times of a T-cell.Immunological reviews · 2010Review
- Apoptotic regulation by MCL-1 through heterodimerization.The Journal of biological chemistry · 2010Article
- Mitochondrial regulation of cell survival and death during low-oxygen conditions.Antioxidants & redox signaling · 2009Review
- Article
- Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Article
- Glucose metabolism attenuates p53 and Puma-dependent cell death upon growth factor deprivation.The Journal of biological chemistry · 2008Article
- Review
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
Abstract
How cells die in the absence of oxygen (anoxia) is not understood. Here we report that cells deficient in Bax and Bak or caspase-9 do not undergo anoxia-induced cell death. However, the caspase-9 null cells do not survive reoxygenation due to the generation of mitochondrial reactive oxygen species. The individual loss of Bim, Bid, Puma, Noxa, Bad, caspase-2, or hypoxia-inducible factor 1beta, which are potential upstream regulators of Bax or Bak, did not prevent anoxia-induced cell death. Anoxia triggered the loss of the Mcl-1 protein upstream of Bax/Bak activation. Cells containing a mitochondrial DNA cytochrome b 4-base-pair deletion ([rho(-)] cells) and cells depleted of their entire mitochondrial DNA ([rho(0)] cells) are oxidative phosphorylation incompetent and displayed loss of the Mcl-1 protein under anoxia. [rho(0)] cells, in contrast to [rho(-)] cells, did not die under anoxia. However, [rho(0)] cells did undergo cell death in the presence of the Bad BH3 peptide, an inhibitor of Bcl-X(L)/Bcl-2 proteins. These results indicate that [rho(0)] cells survive under anoxia despite the loss of Mcl-1 protein due to residual prosurvival activity of the Bcl-X(L)/Bcl-2 proteins. Collectively, these results demonstrate that anoxia-induced cell death requires the loss of Mcl-1 protein and inhibition of the electron transport chain to negate Bcl-X(L)/Bcl-2 proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.