Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)

Journal article

The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff and other mitochondrial outer membrane proteins to facilitate the removal of defective mitochondria and maintain the integrity of the mitochondrial network. Here we show that, in addition to this clearance pathway, Parkin also ubiquitinates Mff in a PINK1-dependent manner under non-stressed conditions to regulate constitutive Mff turnover. We further show that removing Parkin via shRNA-mediated knockdown does not completely prevent Mff ubiquitination under these conditions, indicating that at least one other ubiquitin ligase contributes to Mff proteostasis. These data suggest that that Parkin plays a role in physiological maintenance of mitochondrial membrane protein composition in unstressed cells through constitutive low-level activation.

Authors: Lee, L; Seager, R; Nakamura, Y; Wilkinson, KA; Henley, JM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS One
• Volume: 14
• Issue: 5
• Article number: e0213116
• Place of publication: United States
• Publication date: 2019-05-21
• Acceptance date: 2019-05-06
• DOI: 10.1371/journal.pone.0213116
• EISSN: 1932-6203
• ISSN: 1932-6203
• Pmid: 31112535
• Language: English
• Keywords: ubiquitination; HEK293 cells; ubiquitin-protein ligases; mitochondrial dynamics; proteolysis; humans; lysosomes; protein kinases; membrane proteins; cell culture techniques; signal transduction; gene knockdown techniques; FFR; mitochondrial proteins