How could Parkin-mediated ubiquitination of mitofusin promote mitophagy?
Much evidence links mitochondrial dysfunction to the death of neurons in Parkinson disease (PD), and is particularly emphasized by our growing understanding of the function of genes linked to recessively inherited PD such as PINK1, parkin and DJ-1. Recent work has revealed an exciting link between the PINK1-Parkin pathway and the autophagic turnover of dysfunctional mitochondrial (mitophagy). We have recently shown that mitofusin is ubiquitinated by Parkin when it is recruited to dysfunctional mitochondria. Recent work also shows that regulated fission and fusion events help segregate dysfunctional mitochondria prior to mitophagy. Here we hypothesize how Parkin-mediated ubiquitination of Mfn may play a role in this mechanism.
Ziviani
Elena
E
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
Whitworth
Alexander J
AJ
D000818:Animals; D004331:Drosophila melanogaster / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D024101:Mitochondrial Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein