PINK1 regulated mitophagy is evident in skeletal muscles.

Autor: Singh F; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.; Department of Physiology, Biomedical Center, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Wilhelm L; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Prescott AR; Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee, UK., Ostacolo K; Department of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Zhao JF; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Ogmundsdottir MH; Department of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Ganley IG; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Jazyk: angličtina
Zdroj: Autophagy reports [Autophagy Rep] 2024 Mar 11; Vol. 3 (1), pp. 2326402.
DOI: 10.1080/27694127.2024.2326402
Abstrakt: PINK1, mutated in familial forms of Parkinson's disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo , we used mito -QC mice in which loss of PINK1 was combined with the mitochondrial-associated POLG D257A mutation. We focused on skeletal muscle as gene expression data indicates that this tissue has the highest PINK1 levels. We found that loss of PINK1 in oxidative hindlimb muscle significantly reduced mitophagy. Of interest, the presence of the POLG D257A mutation, while having a minor effect in most tissues, restored levels of muscle mitophagy caused by the loss of PINK1. Although our observations highlight that multiple mitophagy pathways operate within a single tissue, we identify skeletal muscle as a tissue of choice for the study of PINK1-dependant mitophagy under basal conditions.
Competing Interests: Disclosure statement IGG is a consultant for Mitobridge Inc.
Databáze: MEDLINE