Finally, while there may be differences between the mechanism of mitochondrial dysfunction observed across familial models of PD in transgenic or knockout mice or iPSC-derived neurons (e.g. LRRK2-G2019S, PINK1-KO, DJ-1-KO), there is considerable agreement that a significant decrease in complex I activity, which is not caused by differences in protein levels, has been consistently observed in postmortem brain tissue from PD humans and contributes to decreased mitochondrial-derived ATP production and enhanced oxidative stress in PD [199]. This evidence concerns the gene PINK1 and Parkinson disease.