Matic I, Strobbe D, Di Guglielmo F, Campanella M
University of Rome Tor Vergata, Rome, Italy.
Regina Elena-National Cancer Institute, Rome, Italy.
Int Rev Cell Mol Biol. 2017;332:233-258. doi: 10.1016/bs.ircmb.2016.12.003. Epub 2017 Feb 23.
The homeostasis of eukaryotic cells relies on efficient mitochondrial function. The control of mitochondrial quality is framed by the combination of distinct but interdependent mechanisms spanning biogenesis, regulation of dynamic network, and finely tuned degradation either through ubiquitin-proteasome system or autophagy (mitophagy). There is continuous evolution on the pathways orchestrating the mitochondrial response to stress signals and the organelle adaptation to quality control during acute and subtle dysfunctions. Notably, it remains indeed ill-defined whether active mitophagy leads to cell survival or death by defective mitochondrial degradation. Above all, uncharted is whether and how pharmacologically tackle these mechanisms may lead to conceive novel therapeutic strategies for treating conditions associated with the defective mitochondria. Here, we attempt to provide a chronological and comprehensive overview of the determining discoveries, which have led to the current knowledge of mitophagy.
真核细胞的稳态依赖于高效的线粒体功能。线粒体质量的控制是由一系列独特但相互依存的机制共同构成的，这些机制涵盖生物发生、动态网络调控以及通过泛素-蛋白酶体系统或自噬（线粒体自噬）进行的精细降解。在急性和轻微功能障碍期间，协调线粒体对应激信号的反应以及细胞器对质量控制的适应的途径一直在不断演变。值得注意的是，活跃的线粒体自噬通过有缺陷的线粒体降解导致细胞存活还是死亡，这一点确实仍不明确。最重要的是，药理学上是否以及如何应对这些机制可能会导致构思出治疗与线粒体缺陷相关病症的新治疗策略，这一点尚不清楚。在此，我们试图按时间顺序并全面地概述那些决定性的发现，这些发现促成了我们目前对线粒体自噬的认识。
