Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation

• The DESE439K mutation disrupts cardiomyocyte cytoarchitecture, including cell size and morphology, and leads to mitochondrial dysfunction. • Mutant cardiomyocytes exhibit impaired mitochondrial architecture, respiratory capacity, and metabolic activity, mirroring defects in patient heart tissue. • Transfer of normal mitochondria into mutant cardiomyocytes restores mitochondrial and contractile functions, highlighting a potential therapeutic strategy. • This study provides a human iPSC-derived cardiomyocyte model for desmin-related cardiomyopathy, enabling mechanistic studies and drug testing.