TY  - JOUR
AU  - Lechado Terradas, Anna
AU  - Zittlau, Katharina I
AU  - Macek, Boris
AU  - Fraiberg, Milana
AU  - Elazar, Zvulun
AU  - Kahle, Philipp J
TI  - Regulation of mitochondrial cargo-selective autophagy by posttranslational modifications.
JO  - The journal of biological chemistry
VL  - 297
IS  - 5
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - DZNE-2022-00092
SP  - 101339
PY  - 2021
AB  - Mitochondria are important organelles in eukaryotes. Turnover and quality control of mitochondria are regulated at the transcriptional and posttranslational level by several cellular mechanisms. Removal of defective mitochondrial proteins is mediated by mitochondria resident proteases or by proteasomal degradation of individual proteins. Clearance of bulk mitochondria occurs via a selective form of autophagy termed mitophagy. In yeast and some developing metazoan cells (e.g., oocytes and reticulocytes), mitochondria are largely removed by ubiquitin-independent mechanisms. In such cases, the regulation of mitophagy is mediated via phosphorylation of mitochondria-anchored autophagy receptors. On the other hand, ubiquitin-dependent recruitment of cytosolic autophagy receptors occurs in situations of cellular stress or disease, where dysfunctional mitochondria would cause oxidative damage. In mammalian cells, a well-studied ubiquitin-dependent mitophagy pathway induced by mitochondrial depolarization is regulated by the mitochondrial protein kinase PINK1, which upon activation recruits the ubiquitin ligase parkin. Here, we review mechanisms of mitophagy with an emphasis on posttranslational modifications that regulate various mitophagy pathways. We describe the autophagy components involved with particular emphasis on posttranslational modifications. We detail the phosphorylations mediated by PINK1 and parkin-mediated ubiquitylations of mitochondrial proteins that can be modulated by deubiquitylating enzymes. We also discuss the role of accessory factors regulating mitochondrial fission/fusion and the interplay with pro- and antiapoptotic Bcl-2 family members. Comprehensive knowledge of the processes of mitophagy is essential for the understanding of vital mitochondrial turnover in health and disease.
KW  - Animals
KW  - Mitochondria: genetics
KW  - Mitochondria: metabolism
KW  - Mitochondrial Dynamics
KW  - Mitochondrial Proteins: genetics
KW  - Mitochondrial Proteins: metabolism
KW  - Mitophagy
KW  - Signal Transduction
KW  - Ubiquitination
KW  - autophagy (Other)
KW  - mitochondria (Other)
KW  - phosphorylation (Other)
KW  - protein kinase PINK1 (Other)
KW  - ubiquitin ligase parkin (Other)
KW  - ubiquitylation (Other)
KW  - Mitochondrial Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34688664
C2  - pmc:PMC8591368
DO  - DOI:10.1016/j.jbc.2021.101339
UR  - https://pub.dzne.de/record/163312
ER  -