TAp73 缺失通过代谢失调加速衰老。
TAp73 depletion accelerates aging through metabolic dysregulation.
机构信息
Medical Research Council, Toxicology Unit, Leicester University, Leicester, United Kingdom.
出版信息
Genes Dev. 2012 Sep 15;26(18):2009-14. doi: 10.1101/gad.197640.112.
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.
摘要
衰老是与活性氧（ROS）清除能力受损有关。在这里，我们表明，p53 家族成员 TAp73 通过调节线粒体活性和防止 ROS 积累来防止衰老。TAp73 缺失的小鼠表现出更明显的衰老，伴有氧化损伤和衰老增加。TAp73 缺失会降低细胞内的 ATP 水平、耗氧量和线粒体复合物 IV 活性，同时增加 ROS 生成和氧化应激敏感性。我们表明，线粒体复合物 IV 亚基细胞色素 C 氧化酶亚基 4（Cox4i1）是 TAp73 的直接靶标，并且 Cox4i1 的敲低可模拟 TAp73 缺失细胞的细胞衰老。结果表明，TAp73 影响线粒体呼吸和 ROS 动态平衡，从而调节衰老。
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