TAp73 depletion accelerates aging through metabolic dysregulation
TAp73 depletion accelerates aging through metabolic dysregulation
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DOI：
10.1101/gad.197640.112
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发表时间：
2012-09-15
影响因子：
10.5
通讯作者：
Mak, Tak Wah
中科院分区：
文献类型：
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作者：
Rufini, Alessandro;Niklison-Chirou, Maria Victoria;Mak, Tak Wah
衰老与活性氧（ROS）清除受损有关。在这里，我们表明，TAp73，p53家族成员，通过调节线粒体活性和防止ROS积累来防止衰老。TAp73缺失小鼠显示出更明显的衰老，伴随着增加的氧化损伤和衰老。TAp73缺失降低细胞ATP水平、耗氧量和线粒体复合物IV活性，增加ROS产生和氧化应激敏感性。我们发现，线粒体复合物IV亚基细胞色素C氧化酶亚基4（Cox4i1）是一个直接的TAp73目标和Cox4i1敲低phenocopies的TAp73无效细胞的细胞衰老。结果表明，TAp73影响线粒体呼吸和ROS稳态，从而调节衰老。
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.