Although this observation is well supported by deleterious mtDNA mutations affecting CIV, ATP synthase or tRNAs, like the A3243G tRNALeu mutation causing MELAS syndrome or the A8344G tRNALys mutation causing MERRF syndrome41,42, CI gene mutations lead to symptomatic mt-myopathies at much lower thresholds. Here, NDUFB6 is linked to MERRF.