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Title: Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling

Abstract

Highlights: Black-Right-Pointing-Pointer Mitofilin deficiency caused disruption of the cristae structures in HeLa cells. Black-Right-Pointing-Pointer Mitofilin deficiency reduced cell proliferation and increased cell sensitivity to apoptotic stimuli. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated the release of cytochrome c from mitochondria. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated STS-induced intrinsic apoptotic pathway without interfering with the activation of Bax. -- Abstract: Mitochondria amplify caspase-dependent apoptosis by releasing proapoptotic proteins, especially cytochrome c. This process is accompanied by mitochondrial cristae remodeling. Our studies demonstrated that mitofilin, a mitochondrial inner membrane protein, acted as a cristae controller to regulate cytochrome c release during apoptosis. Knockdown of mitofilin in HeLa cells with RNAi led to fragmentation of the mitochondrial network and disorganization of the cristae. Mitofilin-deficient cells showed cytochrome c redistribution between mitochondrial cristae and the intermembrane space (IMS) upon intrinsic apoptotic stimuli. In vitro cytochrome c release experiments further confirmed that, compared with the control group, tBid treatment led to an increase in cytochrome c release from mitofilin-deficient mitochondria. Furthermore, the cells with mitofilin knockdown were more prone to apoptosis by accelerating cytochrome c release upon the intrinsic apoptotic stimuli than controls. Moreover, mitofilin deficiency did not interfere with the activation of proapoptotic member Bax upon intrinsic apoptotic stimuli.more » Thus, mitofilin distinctly functions in cristae remodeling and controls cytochrome c release during apoptosis.« less

Authors:
; ; ; ;  [1];  [1];  [1]
  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5 Dong Dan San Tiao, Beijing 100005 (China)
Publication Date:
OSTI Identifier:
22210322
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 428; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL PROLIFERATION; HELA CELLS; IN VITRO; MEMBRANE PROTEINS; MITOCHONDRIA; SENSITIVITY; STIMULI

Citation Formats

Yang, Rui-feng, Zhao, Guo-wei, Liang, Shu-ting, Zhang, Yuan, Sun, Li-hong, Chen, Hou-zao, E-mail: houzao@gmail.com, and Liu, De-pei, E-mail: liudp@pumc.edu.cn. Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.10.012.
Yang, Rui-feng, Zhao, Guo-wei, Liang, Shu-ting, Zhang, Yuan, Sun, Li-hong, Chen, Hou-zao, E-mail: houzao@gmail.com, & Liu, De-pei, E-mail: liudp@pumc.edu.cn. Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling. United States. doi:10.1016/J.BBRC.2012.10.012.
Yang, Rui-feng, Zhao, Guo-wei, Liang, Shu-ting, Zhang, Yuan, Sun, Li-hong, Chen, Hou-zao, E-mail: houzao@gmail.com, and Liu, De-pei, E-mail: liudp@pumc.edu.cn. Fri . "Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling". United States. doi:10.1016/J.BBRC.2012.10.012.
@article{osti_22210322,
title = {Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling},
author = {Yang, Rui-feng and Zhao, Guo-wei and Liang, Shu-ting and Zhang, Yuan and Sun, Li-hong and Chen, Hou-zao, E-mail: houzao@gmail.com and Liu, De-pei, E-mail: liudp@pumc.edu.cn},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Mitofilin deficiency caused disruption of the cristae structures in HeLa cells. Black-Right-Pointing-Pointer Mitofilin deficiency reduced cell proliferation and increased cell sensitivity to apoptotic stimuli. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated the release of cytochrome c from mitochondria. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated STS-induced intrinsic apoptotic pathway without interfering with the activation of Bax. -- Abstract: Mitochondria amplify caspase-dependent apoptosis by releasing proapoptotic proteins, especially cytochrome c. This process is accompanied by mitochondrial cristae remodeling. Our studies demonstrated that mitofilin, a mitochondrial inner membrane protein, acted as a cristae controller to regulate cytochrome c release during apoptosis. Knockdown of mitofilin in HeLa cells with RNAi led to fragmentation of the mitochondrial network and disorganization of the cristae. Mitofilin-deficient cells showed cytochrome c redistribution between mitochondrial cristae and the intermembrane space (IMS) upon intrinsic apoptotic stimuli. In vitro cytochrome c release experiments further confirmed that, compared with the control group, tBid treatment led to an increase in cytochrome c release from mitofilin-deficient mitochondria. Furthermore, the cells with mitofilin knockdown were more prone to apoptosis by accelerating cytochrome c release upon the intrinsic apoptotic stimuli than controls. Moreover, mitofilin deficiency did not interfere with the activation of proapoptotic member Bax upon intrinsic apoptotic stimuli. Thus, mitofilin distinctly functions in cristae remodeling and controls cytochrome c release during apoptosis.},
doi = {10.1016/J.BBRC.2012.10.012},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 428,
place = {United States},
year = {2012},
month = {11}
}