Research into novel therapies of mitochondrial disease has been hampered by the lack of useful noninvasive biomarkers that measure disease severity and progression.9,10 Our findings suggest that PET imaging of TSPO has potential as a noninvasive biomarker of disease progression for CNS involvement in mitochondrial disease, given that binding abnormalities across the entire brain were significantly correlated with clinical severity. Here, TSPO is linked to mitochondrial disease.