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Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

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Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c

release

Yushan Zhu;Min Li;Xiaohui Wang;Haijing Jin;Shusen Liu;Jianxin Xu;Quan Chen

【期刊名称】《细胞研究(英文版)》 【年(卷),期】2012(022)001

【摘要】Mitochondrial catastrophe can be the cause or consequence of apoptosis and is associated with a number of pathophysiological conditions.The exact relationship between mitochondrial catastrophe and caspase activation is not completely understood.Here we addressed the underlying mechanism,explaining how activated caspase could feedback to attack mitochondria to amplify further cytochrome e (cyto.c) release.We discovered that cytochrome c1 (cyto.c1) in the bc1 complex of the mitochondrial respiration chain was a novel substrate of caspase 3 (casp.3).We found that cyto.c1 was cleaved at the site of D106,which is critical for binding with cyto.c,following apoptotic stresses or targeted expression of casp.3 into tbe mitochondrial intermembrane space.We demonstrated that this cleavage was closely linked with further cyto.c release and mitochondrial catastrophe.These mitochondrial events could be effectively blocked by expressing non-cleavable cyto.c1 (D106A) or by caspase inhibitor z-VAD-fmk.Our results demonstrate that the cleavage of cyto.c1 represents a critical step for the feedback

amplification of cyto.c release by caspases and subsequent mitochondrial catastrophe. 【总页数】15页(127-141) 【关键词】

【作者】Yushan Zhu;Min Li;Xiaohui Wang;Haijing Jin;Shusen Liu;Jianxin Xu;Quan Chen

【作者单位】The Joint Laboratory of Apoptosis and Cancer Biology, The National

Key

Laboratory

of

Biomembrane

and

Membrane

Biotechnology, Chinese Academy of Sciences, Beijing 100101, China;College of Life Sciences, Nankai University, Tianjin 300071, China;Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;The Joint Laboratory of Apoptosis and Cancer Biology, The National Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Beijing 100101, China;College of Life Sciences, Nankai University, Tianjin 300071, China;The Joint Laboratory of Apoptosis and Cancer Biology, The National

Key

Laboratory

of

Biomembrane

and

Membrane

Biotechnology, Chinese Academy of Sciences, Beijing 100101, China;College of Life Sciences, Nankai University, Tianjin 300071, China;The Joint Laboratory of Apoptosis and Cancer Biology, The National

Key

Laboratory

of

Biomembrane

and

Membrane

Biotechnology, Chinese Academy of Sciences, Beijing 100101,

China;College of Life Sciences, Nankai University, Tianjin 300071, China;Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;The Joint Laboratory of Apoptosis and Cancer Biology, The National Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Beijing 100101, China;College of Life Sciences, Nankai University, Tianjin 300071, China 【正文语种】中文 【中图分类】 【文献来源】

https://www.zhangqiaokeyan.com/academic-journal-cn_cell-research-english_thesis/0201255251289.html 【相关文献】

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Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

Caspasecleavageofcytochromec1disruptsmitochondrialfunctionandenhancescytochromecreleaseYushanZhu;MinLi;XiaohuiWang;HaijingJin;ShusenLiu;JianxinXu;QuanChen<
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