Table 1.

Familial PD genes and their potential role in mitochondrial dysfunction (modified from [5])

Genes	Associated mitochondrial dysfunction	References
α-synuclein (Park1/4)	Reduced Complex I activity and oxygen consumption rate Abnormal mitochondrial morphology, Ca2+ dyshomeostasis Abnormal ER-mitochondria transport	[6–8]
Parkin (Park2)	Reduced mitochondrial respiration, oxidative damage Mitochondrial functional integrity Reduced mitochondrial biogenesis Abnormal mitochondria High mitochondrial ROS	[9–12]
PINK1 (Park6)	Reduced electron transfer cascade enzyme function Reduced ATP production, Ca2+ dyshomeostasis Reduced mitochondrial function, fission Abnormal mitochondria and high mitochondrial ROS Abnormal mitochondrial Ca2+ handling	[12–16]
DJ1 (Park7)	Abnormal mitochondrial morphology Uncoupled mitochondria Glycolytic shift Mutants induce mitochondrial fragmentation	[17–19]
LRRK2 (Park8)	Reduced ATP production and membrane potential Abnormal mitochondrial fission/fusion Delayed Miro degradation and mitophagy	[20–22]
ATP13A2 (Park9)	Mutant causes low mitochondrial oxygen consumption rate, reduced ATP synthesis	[23]
HTRA2 (Park13)	Mitochondrial morphological abnormalities Low respiration, increased sensitivity to apoptosis	[24, 25]
FBXO7 (Park15)	Impaired ubiquitin-proteasome system, reduced mitophagy leading to accumulation of dysfunctional mitochondria Mitochondrial accumulation of aggregates	[26, 27]
VPS35 Park17	Mitochondrial fragmentation, reduced oxygen consumption	[28]
CHCHD2 (Park22)	Decreased complex I activity, respiration, increased ROS transcription factor for complex IV subunit cytochrome c oxidase 4I2 Dysregulated apoptosis	[29–31]
PLA2G6	Decreased mitochondrial membrane potential and function	[32]
GBA	Reduced macro-autophagy leading to accumulation of dysfunctional mitochondria	[33]

PD, Parkinson’s disease; ER, endoplasmic reticulum; ROS, reactive oxygen species; ATP, adenosine triphosphate