TAp73 depletion accelerates aging through metabolic dysregulation

Alessandro Rufini, Maria Victoria Niklison-Chirou, Satoshi Inoue, Richard Tomasini, Isaac S. Harris, Arianna Marino, Massimo Federici, David Dinsdale, Richard A. Knight, Gerry Melino, Tak Wah Mak

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)


Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.

Original languageEnglish
Pages (from-to)2009-2014
Number of pages6
JournalGenes and Development
Issue number18
Publication statusPublished - 2012 Sept 15
Externally publishedYes


  • Aging
  • Metabolism
  • Mitochondria
  • P53
  • P73
  • ROS
  • Senescence

ASJC Scopus subject areas

  • General Medicine


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