Postdoc Fellowships 2026 - Project 4

Summary

A hallmark feature of type 2 diabetes is reduced skeletal muscle mitochondrial content. Exercise improves mitochondrial volume and quality, however emerging evidence from our laboratory suggests that this may be compromised in individuals with type 2 diabetes. The purpose of this project is to define the molecular mechanisms underlying defective mitophagy in type 2 diabetes. By using exercise as a physiological perturbation, this work will establish how mitochondrial quality control is regulated in human skeletal muscle, and how this regulation is altered in type 2 diabetes. Specifically, this project will investigate whether the mitophagy receptor optineurin contributes to exercise-stimulated mitochondrial quality control and metabolic flexibility in skeletal muscle. Furthermore, we will investigate how distinct optineurin phosphorylation signatures, that emerge after exercise in individuals with and without type 2 diabetes, regulate optineurin function and therefore mitophagy. These studies will define how optineurin regulates skeletal muscle mitophagy and reveal a mechanism underlying impaired mitochondrial quality control in type 2 diabetes, identifying a potential therapeutic target to restore metabolic flexibility.