Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity

被引：250

作者：

Shimizu, S ^{[1
]}

Tsujimoto, Y ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Biomed Res Ctr, Dept Med Genet,CREST Japan Sci & Technol Corp JST, Suita, Osaka 5650871, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 02期

关键词：

D O I：

10.1073/pnas.97.2.577

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic Bcl-2 family members such as Bax and Bak induce apoptogenic mitochondrial cytochrome c release and membrane potential (Delta phi) loss in isolated mitochondria. Using isolated mitochondria, we showed that Bid and Bik, BH3-only proteins from the Bcl-2 family, induced cytochrome c release but not Delta phi loss. Unlike Bax/Bak, the cytochrome c release induced by Bid/Bik was Ca2+-independent, cyclosporin A-insensitive, and respiration-independent. Furthermore, in contrast to Bax/Bak, Bid/Bik neither interacted with VDAC nor directly affected the VDAC activity in liposomes, Consistently, Bid/Bik induced apoptosis without Delta phi loss, whereas Bax induced apoptosis with Delta phi loss. These findings indicated the involvement of a different mechanism in BH3-only, protein-induced apoptogenic cytochrome c release.

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页码：577 / 582

页数：6

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