Mutations in mitochondrial genes cause diverse multi-systemic disorders that affect energy metabolism. I will discuss how a specific genetic mutation characterised by developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias along with severe metabolic crises causes multi-organelle defects and unravel the molecular function of the protein it encodes. Loss of the pathogenic gene in cells causes impairs intermediate filament structure, resulting in fragmented mitochondrial networks and formation of cup-like mitochondria identified by focused ion beam scanning electron microscopy (FIB-SEM). In mice loss of the pathogenic gene causes heart defects, reduced muscle function and hypoglycemia that were caused by remodelling of cytoskeletal structure, resulting in changes in the mitochondrial and cytoplasmic proteomes and post-translational modifications. We identify the molecular mechanisms of a protein whose function has been elusive, providing new therapeutic options and drug targets.