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

Publication ,  Journal Article
Yuan, L; Zhai, L; Qian, L; Huang, D; Ding, Y; Xiang, H; Liu, X; Thompson, JW; Liu, J; He, Y-H; Chen, X-Q; Hu, J; Kong, Q-P; Tan, M; Wang, X-F
Published in: Cell Res
June 2018

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.

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Published In

Cell Res

DOI

EISSN

1748-7838

Publication Date

June 2018

Volume

28

Issue

6

Start / End Page

625 / 643

Location

England

Related Subject Headings

  • Signal Transduction
  • Oxidative Stress
  • Mice, Inbred C57BL
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells
  • Glycerolphosphate Dehydrogenase
  • Endopeptidases
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
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Yuan, L., Zhai, L., Qian, L., Huang, D., Ding, Y., Xiang, H., … Wang, X.-F. (2018). Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death. Cell Res, 28(6), 625–643. https://doi.org/10.1038/s41422-018-0043-5
Yuan, Lifeng, Linhui Zhai, Lili Qian, De Huang, Yi Ding, Handan Xiang, Xiaojing Liu, et al. “Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.Cell Res 28, no. 6 (June 2018): 625–43. https://doi.org/10.1038/s41422-018-0043-5.
Yuan L, Zhai L, Qian L, Huang D, Ding Y, Xiang H, et al. Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death. Cell Res. 2018 Jun;28(6):625–43.
Yuan, Lifeng, et al. “Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.Cell Res, vol. 28, no. 6, June 2018, pp. 625–43. Pubmed, doi:10.1038/s41422-018-0043-5.
Yuan L, Zhai L, Qian L, Huang D, Ding Y, Xiang H, Liu X, Thompson JW, Liu J, He Y-H, Chen X-Q, Hu J, Kong Q-P, Tan M, Wang X-F. Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death. Cell Res. 2018 Jun;28(6):625–643.

Published In

Cell Res

DOI

EISSN

1748-7838

Publication Date

June 2018

Volume

28

Issue

6

Start / End Page

625 / 643

Location

England

Related Subject Headings

  • Signal Transduction
  • Oxidative Stress
  • Mice, Inbred C57BL
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells
  • Glycerolphosphate Dehydrogenase
  • Endopeptidases
  • Developmental Biology