Patient-derived induced pluripotent stem cell models reveal mechanistic links between aberrant mitochondrial dynamics and cardiomyopathy.

Abstract

DNM1L mutations impair mitochondrial fission, leading to cardiomyocyte energy deficits and contractile dysfunction, and reveal a cardiac role for DNM1L beyond neurological disease. iPSC-cardiomyocytes derived from patients with DNM1L mutations demonstrate mitochondrial defects and cardiomyopathy phenotypes, offering a robust model to dissect disease mechanisms and identify personalised therapies. Disrupted mitochondrial dynamics directly lead to calcium mishandling and contractile dysfunction, positioning fission/fusion pathways as promising therapeutic targets in cardiomyopathy treatment.