The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol

被引:290
作者
Kluck, RM
Esposti, MD
Perkins, G
Renken, C
Kuwana, T
Bossy-Wetzel, E
Goldberg, M
Allen, T
Barber, MJ
Green, DR
Newmeyer, DD [1 ]
机构
[1] La Jolla Inst Allergy Immunol, Div Cellular Immunol, 10355 Sci Ctr Dr, San Diego, CA 92121 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[3] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA
[4] Christie Hosp NHS Trust, Paterson Inst, Manchester M20 9BX, Lancs, England
[5] Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Tampa, FL 33612 USA
关键词
apoptosis; Bid; Bax; cytochrome c; mitochondrial outer membrane;
D O I
10.1083/jcb.147.4.809
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During apoptosis, an important pathway leading to caspase activation involves the release of cytochrome c from the intermembrane space of mitochondria, Using a cell-free system based on Xenopus egg extracts, we examined changes in the outer mitochondrial membrane accompanying cytochrome c efflux. The pro-apoptotic proteins, Bid and Bax, as well as factors present in Xenopus egg cytosol, each induced cytochrome c release when incubated with isolated mitochondria, These factors caused a permeabilization of the outer membrane that allowed the corelease of multiple intermembrane space proteins: cytochrome c, adenylate kinase and sulfite oxidase. The efflux process is thus nonspecific. None of the cytochrome c-releasing factors caused detectable mitochondrial swelling, arguing that matrix swelling is not required for outer membrane permeability in this system. Bid and Bax caused complete release of cytochrome c but only a limited permeabilization of the outer membrane, as measured by the accessibility of inner membrane-associated respiratory complexes III and IV to exogenously added cytochrome c. However, outer membrane permeability was strikingly increased by a macromolecular cytosolic factor, termed PEF (permeability enhancing factor). We hypothesize that PEF activity could help determine whether cells can recover from mitochondrial cytochrome c release.
引用
收藏
页码:809 / 822
页数:14
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