Mitochondrial autophagy: Life and breath if the cell
Mitochondrial autophagy: Life and breath if the cell
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DOI：
10.4161/auto.5956
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发表时间：
2008-05-16
期刊：
影响因子：
13.3
通讯作者：
Semenza, Gregg L.
中科院分区：
文献类型：
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作者：
Semenza, Gregg L.
在所有后生动物物种中，对降低的O2可用性的稳态反应由转录激活因子缺氧诱导因子I（HIF-1）调节。对持续缺氧的一个重要适应是线粒体呼吸的主动抑制。在小鼠胚胎成纤维细胞中，HIF-1诱导BNIP 3的表达，其触发选择性线粒体自噬。当暴露于缺氧时，HIF-1缺陷细胞不诱导BNIP 3或自噬，不降低线粒体质量或下调呼吸，并且由于活性氧的毒性水平而在72小时内死亡。这些研究表明线粒体。自噬代表了对缺氧的适应性代谢反应，其是维持氧化还原稳态和细胞存活所必需的。
Homeostatic responses to reduced 02 availability are regulated by the transcriptional activator hypoxia-inducible factor I (HIF-1) in all metazoan species. An essential adaptation to sustained hypoxia is an active repression of mitochondrial respiration. In mouse embryo fibroblasts, HIF-1 induces expression of BNIP3, which triggers selective mitochondrial autophagy, When exposed to hypoxia, HIF-1-deficient cells do not induce BNIP3 or autophagy, do not decrease mitochondrial mass or downregulate respiration, and die within 72 hours due to toxic levels of reactive oxygen species. These studies indicate that mitochondrial. autophagy represents an adaptive metabolic response to hypoxia that is necessary to maintain redox homeostasis and cell survival.