In summary, we identified for the first time a direct interaction of Omi/HtrA2 with OPA1, a regulatory component of the mitochondrial fusion machinery, and demonstrate consequences of loss of Omi/HtrA2 function on mitochondrial dynamics and integrity that are relevant for different neurodegenerative disorders like Parkinson's and Huntington's disease. The gene discussed is HTRA2; the disease is Huntington disease.