Málstofa Lífvísindaseturs - PINK1 regulated mitophagy is evident in skeletal muscles

Málstofa Lífvísindaseturs Thursday February 12 at 12:30 - 13:10 in Árnagarður, stofu 306 

Speaker: Dr. Francois Singh, lektor við Læknadeild, Háskóla Íslands.

Title: PINK1 regulated mitophagy is evident in skeletal muscles

Abstract: 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 POLGD257A 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 POLGD257A 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.

PMID: 38988500
DOI: 10.1080/27694127.2024.2326402

Speaker bio:

Dr. Francois Singh obtained his PhD in Cellular and molecular aspects of Biology in September 2016 from the University of Strasbourg (France). His PhD project was realised in co-direction between the Clinical Pharmacology and Toxicology lab of Professor Stephan Krähenbühl at the University of Basel (Switzerland) and the EA3072: Mitochondria, Oxidative Stress and Muscular Protection Lab of Professor Bernard Geny at the University of Strasbourg (France). He investigated the role of mitochondrial adaptations in statin-induced myotoxicity, focusing on the opposite effect of statins in glycolytic and in oxidative muscles. During that time, he also taught medical students at the University hospital of Strasbourg Physiology, as well as Toxicology students at the Department of Pharmaceutical Sciences in Basel.

In 2017, he joined the lab of Professor Ian Ganley as a postdoctoral research assistant at the MRC-Protein Phosphorylation and ubiquitylation unit, University of Dundee, United Kingdom, in collaboration with GlaxoSmithKline. His project investigated the physiological role of pathogenic mutations involved in Parkinson’s disease on mitophagy and general autophagy in vivo. His work provided the first in vivo evidence that pathogenic LRRK2 directly impairs basal mitophagy and demonstrated that pharmacological inhibition of LRRK2 is a rational mitophagy-rescue approach and potential PD therapy.

In March 2023, Francois has been recruited to the post of Lektor/Assistant Professor by the School of Health Sciences at the University of Iceland to establish his independent laboratory.

His lab is interested in how mitochondrial homeostasis is regulated basally, as well as in pathological contexts. 

Mitochondria are the cell’s main actors in charge of not only energy production, but are also involved in calcium homeostasis regulation, the production and scavenging of free radicals, intracellular pH regulation, heme biosynthesis, lipid biosynthesis and metabolism, ubiquinol and Fe-S centres biosynthesis, steroid hormones production, and in controlling the programmed cell death. These vital functions are dependent on mitochondrial content and quality. Mitochondria are dynamic organelles that can adjust to the cell’s changing needs via a delicate balance between the production of new mitochondria through biogenesis, and their elimination via mitophagy, the autophagy of the mitochondria.