ATM mediated-p53 signaling pathway forms a novel axis for senescence control

Mitochondrion. 2020 Nov:55:54-63. doi: 10.1016/j.mito.2020.09.002. Epub 2020 Sep 17.

Abstract

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration.

Keywords: ATM inhibition; Metabolic reprogrammer; Mitochondria; P53; Senescence alleviation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Cell Line
  • Cell Proliferation
  • Cellular Senescence
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Humans
  • Mitochondria / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins