Volume 22, No 1, Jan 2012

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 22 Issue 1, January 2012: 127-141

ORIGINAL ARTICLES

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

Yushan Zhu^1,2,*, Min Li^3,*, Xiaohui Wang¹, Haijing Jin¹, Shusen Liu1¹, Jianxin Xu³ and Quan Chen^1,2

¹The Joint Laboratory of Apoptosis and Cancer Biology, The National Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Beijing 100101, China
²College of Life Sciences, Nankai University, Tianjin 300071, China
³Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Correspondence: Quan Chen, Jianxin Xu,(chenquan@nankai.edu.cn; xujx@sun5.ibp.ac.cn)

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 c (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 the 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.

Cell Research (2012) 22:127-141. doi:10.1038/cr.2011.82; published online 17 May 2011

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