Seminars

The UPR^mt coordinates mitochondrial network expansion and peroxisome biogenesis in the model organism Caenorhabditis elegans

As organisms develop, individual cells generate mitochondria and peroxisomes to fulfill their physiological requirements. A decline, or dysfunction in these organelles is associated with ageing and a vast array of clinical manifestations including metabolic disorders and neurodegenerative diseases. Despite this, it is unknown how mitochondrial network expansion and peroxisome biogenesis is scaled to cell growth, and what compensatory pathways cells employ to maintain the organelles’ function. The mitochondrial unfolded protein response (UPR^mt) is a signaling pathway mediated by the transcription factor ATFS-1. Using genetic and biochemical approaches in the model organism Caenorhabditis elegans we demonstrate that ATFS-1 mediates an adaptable mitochondrial network expansion and peroxisome biogenesis program that is active throughout normal development. We characterized the molecular mechanism and signaling events that regulate the UPR^mt and uncovered a peroxisomal retrograde response that is required for peroxisome biogenesis. These findings as well as the therapeutic potential and future directions of my studies will be presented.