Although a similar protective mechanism has not yet been identified in humans, the importance of mtDNA copy-number regulation is highlighted by the vulnerability of the substantia nigra in inherited mtDNA-depletion disorders8, 9 and the increased risk of PD associated with genetic variation in genes encoding key factors of mtDNA maintenance, such as the mtDNA polymerase γ (POLG) and mitochondrial transcription factor A (TFAM)10, 11. Here, TFAM is linked to Parkinson disease.