Autophagy and mitophagy in pancreatic β-cell homeostasis and their involvement in diabetes pathophysiology.
Autophagy is an evolutionarily conserved cellular quality control pathway that responds to the metabolic state of the cell, and its dysregulation has been broadly associated with metabolic disorders like diabetes mellitus. Among different types of autophagy, mitophagy or the selective autophagic clearance of dysfunctional mitochondria has emerged as particularly relevant in pancreatic β-cell biology and its pathophysiology. Recent advances in functional genomics and animal studies implicate the autophagy/mitophagy pathway components as effector transcripts at diabetes risk loci, providing a new rationale for investigation of genetic determinants of autophagy/mitophagy in β cells. In this review, we take a β-cell centric perspective to examine the evidence for autophagy/mitophagy across four clinically relevant diabetes categories (type 1, type 2, gestational, and monogenic diabetes) and discuss the functional significance and complexity of these pathways in β-cell failure.