FBS/BSA media concentration determines CCCP’s ability to depolarize mitochondria and activate PINK1-PRKN mitophagy

Soutar, M P M; Kempthorne, L; Annuario, E; Luft, C; Wray, S; Ketteler, R; Ludtmann, M H R; Plun-Favreau, H

Abstract

Mitochondrial quality control is essential for maintaining a healthy population of mitochondria. Two proteins associated with Parkinson disease, the kinase PINK1 and the E3 ubiquitin ligase PRKN, play a central role in the selective degradation of heavily damaged mitochondria (mitophagy), thus avoiding their toxic accumulation. Most of the knowledge on PINK1-PRKN mitophagy comes from in vitro experiments involving the treatment of mammalian cells with high concentrations of mitochondrial uncouplers, such as CCCP. These chemicals have been shown to mediate off target effects, other than mitochondrial depolarization. A matter of controversy between mitochondrial physiologists and cell biologists is the discrepancy between concentrations of CCCP needed to activate mitophagy (usually >10 μM), when compared to the much lower concentrations used to depolarize mitochondria (

Citation

Soutar, M. P. M., Kempthorne, L., Annuario, E., Luft, C., Wray, S., Ketteler, R., Ludtmann, M. H. R., & Plun-Favreau, H. (2019). FBS/BSA media concentration determines CCCP’s ability to depolarize mitochondria and activate PINK1-PRKN mitophagy. Autophagy, https://doi.org/10.1080/15548627.2019.1603549

• Journal Article Type: Letter
• Acceptance Date: Feb 23, 2019
• Publication Date: May 7, 2019
• Deposit Date: May 11, 2019
• Publicly Available Date: May 10, 2020
• Journal: Autophagy
• Print ISSN: 1554-8627
• Electronic ISSN: 1554-8635
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1080/15548627.2019.1603549
• Public URL: https://rvc-repository.worktribe.com/output/1382463