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Genes Dev. 2012 Sep 15;26(18):2009-14. doi: 10.1101/gad.197640.112.

TAp73 depletion accelerates aging through metabolic dysregulation.

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1
Medical Research Council, Toxicology Unit, Leicester University, Leicester, United Kingdom.

Abstract

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.

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PMID:
22987635
PMCID:
PMC3444727
DOI:
10.1101/gad.197640.112
[Indexed for MEDLINE]
Free PMC Article
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