Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow 119991, Russian Federation.
Department of Biological Sciences, Salem University, Salem, WV, 26426, United States.
Curr Neuropharmacol. 2021;19(2):170-192. doi: 10.2174/1570159X18666200522202319.
Mitochondria are essential organelles for healthy eukaryotic cells. They produce energyrich phosphate bond molecules (ATP) through oxidative phosphorylation using ionic gradients. The presence of mitophagy pathways in healthy cells enhances cell protection during mitochondrial damage. The PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent pathway is the most studied for mitophage. In addition, there are other mechanisms leading to mitophagy (FKBP8, NIX, BNIP3, FUNDC1, BCL2L13). Each of these provides tethering of a mitochondrion to an autophagy apparatus via the interaction between receptor proteins (Optineurin, p62, NDP52, NBR1) or the proteins of the outer mitochondrial membrane with ATG9-like proteins (LC3A, LC3B, GABARAP, GABARAPL1, GATE16). Another pathogenesis of mitochondrial damage is mitochondrial depolarization. Reactive oxygen species (ROS) antioxidant responsive elements (AREs) along with antioxidant genes, including pro-autophagic genes, are all involved in mitochondrial depolarization. On the other hand, mammalian Target of Rapamycin Complex 1 (mTORC1) and AMP-dependent kinase (AMPK) are the major regulatory factors modulating mitophagy at the post-translational level. Protein-protein interactions are involved in controlling other mitophagy processes. The objective of the present review is to analyze research findings regarding the main pathways of mitophagy induction, recruitment of the autophagy machinery, and their regulations at the levels of transcription, post-translational modification and protein-protein interaction that appeared to be the main target during the development and maturation of neurodegenerative disorders.
线粒体是健康真核细胞的必需细胞器。它们通过离子梯度利用氧化磷酸化产生高能磷酸盐键分子（ATP）。健康细胞中存在的线粒体自噬途径增强了线粒体损伤时的细胞保护。PTEN 诱导的假定激酶 1（PINK1）/Parkin 依赖性途径是研究线粒体自噬的最主要途径。此外，还有其他导致线粒体自噬的机制（FKBP8、NIX、BNIP3、FUNDC1、BCL2L13）。这些机制中的每一种都通过受体蛋白（Optineurin、p62、NDP52、NBR1）或外膜蛋白与 ATG9 样蛋白（LC3A、LC3B、GABARAP、GABARAPL1、GATE16）之间的相互作用，将线粒体与自噬装置连接起来。线粒体损伤的另一种发病机制是线粒体去极化。活性氧（ROS）抗氧化反应元件（AREs）以及包括自噬促进基因在内的抗氧化基因都参与了线粒体去极化。另一方面，哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）和 AMP 依赖的蛋白激酶（AMPK）是调节线粒体自噬的主要翻译后水平的调节因子。蛋白质-蛋白质相互作用参与控制其他线粒体自噬过程。本综述的目的是分析有关线粒体自噬诱导、自噬机制募集及其在转录、翻译后修饰和蛋白质-蛋白质相互作用水平上的调节的主要途径的研究结果，这些结果似乎是神经退行性疾病发生和成熟过程中的主要目标。
