Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death

doi:10.1038/s41422-018-0043-5

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	Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death
	Yuan, Lifeng 1,2; Zhai, Linhui 3,4; Qian, Lili 3,4; Huang, De 1; Ding, Yi 1; Xiang, Handan 1; Liu, Xiaojing 1; Thompson, J. Will 5; Liu, Juan 1; He, Yong-Han 6
刊名	CELL RESEARCH
	2018-06
卷号	28 期号:6 页码:625-643
ISSN号	1001-0602
DOI	10.1038/s41422-018-0043-5
文献子类	Article
英文摘要	Cellular senescence is a fundamental cell fate playing a significant role throughout the natural aging process. However, the molecular determinants distinguishing senescence from other cell-cycle arrest states such as quiescence and post-mitotic state, and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. Employing multi-omics approaches, we revealed that switching off the specific mitochondrial processing machinery involving the peptidase IMMP2L serves as the foundation of the senescence program, which was also observed during the mammalian aging process. Mechanistically, we demonstrate that IMMP2L processes and thus activates at least two substrates, mitochondrial metabolic enzyme glycerol-3-phosphate dehydrogenase (GPD2) and cell death regulator apoptosis-inducing factor (AIF). For cells destined to senesce, concerted shutdown of the IMMP2L-GPD2 and IMMP2L-AIF signaling axes collaboratively drives the senescent process by reprogramming mitochondria-associated redox status, phospholipid metabolism and signaling network, and simultaneously blocking cell death under oxidative stress conditions.
资助项目	CCSG[P30CA01423] ; Chinese Academy of Sciences[QYZDBSSW-SMC020] ; Chinese Academy of Sciences[152453KYSB20160006] ; Chinese Academy of Sciences[XDA12020314] ; National Basic Research Program of China[2014CBA02004] ; National Institutes of Health[R01-CA154586] ; CTSA[UL1TR001117]
WOS关键词	APOPTOSIS-INDUCING FACTOR ; PLASMINOGEN-ACTIVATOR INHIBITOR-1 ; IN-VIVO ; PYRUVATE-DEHYDROGENASE ; MITOCHONDRIAL CALPAIN ; INTERMEMBRANE SPACE ; STEM-CELLS ; LIFE-SPAN ; CANCER ; LONGEVITY
WOS研究方向	Cell Biology
语种	英语
CSCD记录号	CSCD:6266441
出版者	INST BIOCHEMISTRY & CELL BIOLOGY
WOS记录号	WOS:000434816300006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279728]
专题	化学蛋白质组学研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Wang, Xiao-Fan
作者单位	1.Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA; 2.Duke Univ, Sch Med, Grad Program Mol Canc Biol, Durham, NC 27710 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 5.Duke Univ, Sch Med, Prote & Metabol Shared Resource, Durham, NC 27710 USA; 6.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Yuan, Lifeng,Zhai, Linhui,Qian, Lili,et al. Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death[J]. CELL RESEARCH,2018,28(6):625-643.
APA	Yuan, Lifeng.,Zhai, Linhui.,Qian, Lili.,Huang, De.,Ding, Yi.,...&Wang, Xiao-Fan.(2018).Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.CELL RESEARCH,28(6),625-643.
MLA	Yuan, Lifeng,et al."Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death".CELL RESEARCH 28.6(2018):625-643.