Mitophagy in neurodegeneration and aging.
Mitophagy in neurodegeneration and aging.
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DOI：
10.3389/fgene.2012.00297
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发表时间：
2012
影响因子：
3.7
通讯作者：
Tavernarakis N
中科院分区：
文献类型：
--
作者：
Palikaras K;Tavernarakis N
大自噬是一种细胞分解代谢过程，涉及将细胞质成分隔离到称为自噬体的双膜囊泡中，所述双膜囊泡随后与溶酶体融合，在溶酶体中它们递送其货物用于降解。自噬的主要生理作用是在营养缺乏的条件下回收细胞内组分，从而为细胞提供重要的物质和能量。选择性自噬也发生在营养丰富的条件下，以清除细胞中受损的细胞器或蛋白质聚集体，否则这些细胞器或蛋白质聚集体会损害细胞活力。线粒体自噬是一种选择性的自噬，通过这种自噬，受损或多余的线粒体被清除，以维持适当的线粒体数量和质量控制。虽然线粒体自噬与一般的大自噬途径共享关键的调节因子，但它也涉及特定于线粒体消除的不同步骤。最近的研究结果表明，parkin和磷酸酶和张力蛋白同源物诱导的推定激酶蛋白1（PINK1），这已经牵连在神经退行性疾病，如帕金森氏病的发病机制，也调节线粒体自噬和功能，以维持线粒体稳态。在这里，我们调查的分子机制，管理过程中的线粒体自噬，并讨论其参与的发病和进展的神经退行性疾病在老化。
Macroautophagy is a cellular catabolic process that involves the sequestration of cytoplasmic constituents into double-membrane vesicles known as autophagosomes, which subsequently fuse with lysosomes, where they deliver their cargo for degradation. The main physiological role of autophagy is to recycle intracellular components, under conditions of nutrient deprivation, so as to supply cells with vital materials and energy. Selective autophagy also takes place in nutrient-rich conditions to rid the cell of damaged organelles or protein aggregates that would otherwise compromise cell viability. Mitophagy is a selective type of autophagy, whereby damaged or superfluous mitochondria are eliminated to maintain proper mitochondrial numbers and quality control. While mitophagy shares key regulatory factors with the general macroautophagy pathway, it also involves distinct steps, specific for mitochondrial elimination. Recent findings indicate that parkin and the phosphatase and tensin homolog-induced putative kinase protein 1 (PINK1), which have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease, also regulate mitophagy and function to maintain mitochondrial homeostasis. Here, we survey the molecular mechanisms that govern the process of mitophagy and discuss its involvement in the onset and progression of neurodegenerative diseases during aging.