Taken together, we identified that parkin V380L aggravated the mitophagy-associated depletion of mitochondrial proteins in the presence of polyQ-expanded ataxin-3, indicating detrimental consequences on the molecular and cellular pathology in MJD patients and explaining the observed earlier AAO in homozygous carriers of this parkin variant. The gene discussed is ATXN3; the disease is Spinocerebellar ataxia type 3.