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The Dawn of Mitophagy: What Do We Know by Now?

[ Vol. 19 , Issue. 2 ]

Author(s):

Dmitrii M. Belousov, Elizaveta V. Mikhaylenko, Siva G. Somasundaram, Cecil E. Kirkland* and Gjumrakch Aliev*   Pages 170 - 192 ( 23 )

Abstract:


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.

Keywords:

Mitochondria and mitophagy pathways, healthy cells, factors modulating mitophagy at the post-translational level, autophagy machinery, mitochondria and post-translational modification, protein-protein interaction and mitophagy, risk factors, central nervous system disorders.

Affiliation:

Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow 119991, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow 119991, Department of Biological Sciences, Salem University, Salem, WV, 26426, Department of Biological Sciences, Salem University, Salem, WV, 26426, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow 119991

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