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

doi:10.1101/gad.197640.112

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

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

113 Citations (SciVal)

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.

Original language	English
Pages (from-to)	2009-2014
Number of pages	6
Journal	Genes and Development
Volume	26
Issue number	18
DOIs	https://doi.org/10.1101/gad.197640.112
Publication status	Published - 15 Sept 2012

Keywords

Aging
Metabolism
Mitochondria
P53
P73
ROS
Senescence

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.197640.112

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title = "TAp73 depletion accelerates aging through metabolic dysregulation",

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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AU - Rufini, Alessandro

AU - Niklison-Chirou, Maria Victoria

AU - Inoue, Satoshi

AU - Tomasini, Richard

AU - Harris, Isaac S.

AU - Marino, Arianna

AU - Federici, Massimo

AU - Dinsdale, David

AU - Knight, Richard A.

AU - Melino, Gerry

AU - Mak, Tak Wah

PY - 2012/9/15

Y1 - 2012/9/15

N2 - 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.

AB - 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.

KW - Aging

KW - Metabolism

KW - Mitochondria

KW - P53

KW - P73

KW - ROS

KW - Senescence

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JF - Genes and Development

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TAp73 depletion accelerates aging through metabolic dysregulation

Abstract

Keywords

ASJC Scopus subject areas

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