Table 1 Mitochondria relevant PARK genes

PARK1/4

aSYN

Autosomal dominant

Rapid

Synaptic vesicle release/transmission [58]

Reduced complex 1 function, elevated mitochondrial ROS, impaired ATP-synthase function [59,60,61,62,63,64,65,66].

Age of onset: 30–50 years; Lewy pathology in humans: yes

PARK2

E3-Ubiquitin-protein-Ligase Parkin

Autosomal recessive

Slow

Mitochondrial quality control (mitophagy, fusion and fission, mitochondrial quality control) [67, 68]

Impaired mitophagy, impaired mitochondrial biogenesis, defects of mitochondrial structure [67, 69].

Age of onset: approx. 30 years; Lewy pathology in humans: variable

PARK6

PTEN-induced kinase-1 (PINK1)

Autosomal recessive

Variable

Mitochondrial quality control (mitophagy, fusion and fission, mitochondrial derived vesicles) [67, 70].

Impaired mitophagy, impaired mitochondrial biogenesis, defects of mitochondrial structure, ETC impairment and reduced ATP production, high levels of ROS [71,72,73].

Age of onset: 30–50 years; Lewy pathology in humans: variable

PARK7

Protein deglycase DJ1 (DJ1)

Autosomal recessive

Slow

Counteracting oxidative stress. Additional chaperone activity. Role in ER-mitochondrial calcium homeostasis [74,75,76].

Elevated levels of ROS, decreased mitochondrial membrane potential, altered mitochondrial morphology [77,78,79,80].

Age of onset: 20–40 years; Lewy pathology in humans: yes

PARK8

Leucine-rich repeat kinase 2 (LRRK2)

Autosomal dominant

Fast

Protein with two enzymatic activities (kinase and GTPase) involved in a plethora of cellular signaling [81, 82].

Indirect effect on mitochondria via modulation of lysosomal degradation and cytoskeleton. Also, direct effect causing impaired mitophagy, altered fusion and fission, impaired trafficking and increased ROS [83,84,85,86].

Age of onset: Typically, 50–60 years, albeit early (< 30s) and late (> 80s) onset has been reported [87, 88]. Lewy pathology in humans: variable

PARK9

ATPase type 13A2 (ATP13A2)

Autosomal recessive

Slow

Primary involvement in lysosomal system [89, 90].

Increased ROS and mitochondrial fragmentation, increased aSYN aggregation [91,92,93].

Age of onset: 10–20 years; Lewy pathology in humans: unknown

PARK15

F-box protein 7 (FBXO7)

Autosomal recessive

Rapid

Neuronal role still largely unclear. Might interact with Parkin and promote mitophagy [94, 95].

Impaired mitophagy, decreased complex 1 function [96, 97].

Age of onset: 10–20 years; Lewy pathology in humans: unknown

PARK17

Vacuolar protein sorting 35 homolog (VPS35)

Autosomal dominant

Slow

Part of the cellular retromer complex and relevant for intracellular trafficking. Implicated in generation of mitochondrial derived vesicles and lysosomal degradation [98, 99].

Increased mitochondrial fission and fragmentation, complex 1 impairment [100,101,102,103].

Age of onset: approx. 50 years; Lewy pathology in humans: unknown

PARK22

Coiled-coil-helix-coiled-coil-helix domain containing protein 2 (CHCHD2)

Autosomal dominant

Slow

Mitochondrial protein. Stabilizing effect on cristae structure. Regulating mitochondrial stress response [104, 105].

Abnormal mitochondrial structure, impaired mitochondrial respiration, elevated ROS levels, aggregation of aSYN [106,107,108].

Age of onset: 50 years; Lewy pathology in humans: yes

PARK23

Vacuolar protein sorting 13 homolog C (VPS13C)

Autosomal recessive

Rapid

Lipid transport protein implicated in mitochondrial biogenesis and mitophagy [109, 110].

Abnormal mitochondrial morphology, disturbed mitochondrial membrane potential, increased mitophagy [100].

Age of onset: 20–30 years; Lewy pathology in humans: yes