Title:The Dawn of Mitophagy: What Do We Know by Now?
Volume: 19
Issue: 2
Author(s): Dmitrii M. Belousov, Elizaveta V. Mikhaylenko, Siva G. Somasundaram, Cecil E. Kirkland*Gjumrakch Aliev*
Affiliation:
- Department of Biological Sciences, Salem University, Salem, WV, 26426,United States
- Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow 119991,Russian Federation
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.
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.
