TitleA Small Molecule That Protects the Integrity of the Electron Transfer Chain Blocks the Mitochondrial Apoptotic Pathway
AuthorsJiang, Xian
Li, Li
Ying, Zhengxin
Pan, Chenjie
Huang, Shaoqiang
Li, Lin
Dai, Miaomiao
Yan, Bo
Li, Ming
Jiang, Hui
Chen, She
Zhang, Zhiyuan
Wang, Xiaodong
AffiliationNatl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China.
Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
KeywordsCYTOCHROME-C RELEASE
DOMINANT OPTIC ATROPHY
CELL-DEATH
INDUCED CHANNEL
COMPLEX-II
BAX
MEMBRANE
OPA1
PROTEASE
CRISTAE
Issue Date2016
PublisherMOLECULAR CELL
CitationMOLECULAR CELL.2016,63(2),229-239.
AbstractIn response to apoptotic stimuli, mitochondria in mammalian cells release cytochrome c and other apoptogenic proteins, leading to the subsequent activation of caspases and apoptotic cell death. This process is promoted by the pro-apoptotic members of the Bcl-2 family of proteins, such as Bim and Bax, which, respectively, initiate and execute cytochrome c release from the mitochondria. Here we report the discovery of a small molecule that efficiently blocks Bim-induced apoptosis after Bax is activated on the mitochondria. The cellular target of this small molecule was identified to be the succinate dehydrogenase subunit B (SDHB) protein of complex II of the mitochondrial electron transfer chain (ETC). The molecule protects the integrity of the ETC and allows treated cells to continue to proliferate after apoptosis induction. Moreover, this molecule blocked dopaminergic neuron death and reversed Parkinson-like behavior in a rat model of Parkinson's disease.
URIhttp://hdl.handle.net/20.500.11897/491854
ISSN1097-2765
DOI10.1016/j.molcel.2016.06.016
IndexedSCI(E)
PubMed
Appears in Collections:生命科学学院

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