Tolkovsky Aviva M
Department Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Biochim Biophys Acta. 2009 Sep;1793(9):1508-15. doi: 10.1016/j.bbamcr.2009.03.002. Epub 2009 Mar 13.
Concurrent mitochondrial elimination and autophagy in many systems has led to the proposal that autophagy is the main mechanism of mitochondrial turnover during development and under pathological conditions. The term mitophagy was coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious. Three questions are being debated: 1) Is there a specific removal of mitochondria by autophagy or is it non-selective or inadvertent? 2) What are the signals that drive this process? 3) Does removal of mitochondria increase or decrease cell viability? There is a mounting evidence for specific signals in/on mitochondria that drive mitochondrial removal from cells by autophagy. The process itself may be both selective and non-selective. In yeast, surprisingly, mitochondrial elimination occurs more by microautophagy (intracellular pinocytosis by the vacuolar membrane) than macroautophagy (initiated by stand-alone nascent double membrane structures known as autophagosomes). In mammalian cells, macroautophagy seems most prevalent though tools to study microautophagy are not well developed. Whilst lack of mitophagy seems to be deleterious, understanding the interplay between autophagy, mitochondrial performance, and cell pathology is a much-needed area of research.
在许多系统中,线粒体清除与自噬同时发生,这使得人们提出自噬是发育过程中和病理条件下线粒体更新的主要机制。“线粒体自噬”一词被创造出来用于描述通过自噬选择性清除线粒体的过程,但该过程本身仍存在争议。目前有三个问题正在讨论中:1)线粒体的清除是通过自噬特异性进行的,还是非选择性或偶然发生的?2)驱动这一过程的信号是什么?3)线粒体的清除会增加还是降低细胞活力?越来越多的证据表明,线粒体内部或表面存在特异性信号,这些信号驱动线粒体通过自噬从细胞中被清除。这个过程本身可能兼具选择性和非选择性。令人惊讶的是,在酵母中,线粒体清除更多是通过微自噬(液泡膜的细胞内胞饮作用)而非巨自噬(由独立的新生双膜结构即自噬体引发)发生的。在哺乳动物细胞中,巨自噬似乎最为普遍,不过用于研究微自噬的工具尚不完善。虽然线粒体自噬的缺失似乎有害,但理解自噬、线粒体功能和细胞病理之间的相互作用是一个急需开展研究的领域。