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

Journal Article · Fri Nov 09 04:00:00 EST 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.10.012· OSTI ID:22210322

Yang, Rui-feng; Zhao, Guo-wei; Liang, Shu-ting; Zhang, Yuan; Sun, Li-hong ^[1]; Chen, Hou-zao ^[1]; Liu, De-pei ^[1]

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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)

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.

• OSTI ID: 22210322
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 428; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
HELA CELLS
IN VITRO
MEMBRANE PROTEINS
MITOCHONDRIA
SENSITIVITY
STIMULI