Mitophagy: What, Why, Where and How?
Welcome to the next CanCell seminar scheduled for Thursday 4th of October at 12:15 hrs.
Speaker: Dr. Ian Ganley, The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Scotland
Mitophagy: What, Why, Where and How? by Dr. Ian Ganley
Mitophagy, the autophagy of mitochondria, is thought to be an essential quality control (QC) mechanism of pathophysiological relevance in mammals with strong links to diseases such as Parkinson’s and cancer. However, if and how mitophagy proceeds within specific cellular subtypes in vivo has remained unclear, largely due to a lack of tractable tools and models. To address this, we developed “mito-QC”, a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mammalian mitophagy and mitochondrial architecture in vivo. mito-QC revealed that mitophagy is a significant process in most tissues, even under basal conditions. Though, within tissues it can be spatially restricted to distinct cell types, particularly those with high metabolic demands such as proximal tubule cells in the kidney or dopaminergic neurons in the midbrain. We are now exploring how these pathways are regulated molecularly and surprisingly, the mechanisms behind these instances of basal mitophagy are distinct from the classical starvation-induced autophagy pathway as well as the canonical PINK1-Parkin mediated pathway.