Mitochondrial Dysfunction in Parkinson's Disease

Table 1

Summary of mutations and links to mitochondrial dysfunction and PD.

Mutation	Link to mitochondria	Links with PD
α-synuclein	Targeted to IMM and causes CI inhibition	(i) Major component of LBs; (ii) Mutation linked with PD
Parkin	Suggested role in mitochondrial function and antioxidant protection	Mutation linked to autosomal recessive juvenile PD
PINK1	Interaction with Parkin	Loss of kinase mutation linked to familial PD
DJ-1	(i) Antioxidant present in mitochondria; (ii) Rescues mitochondria from PINK1 deletion	Mutation linked with numerous cases of familial PD
Omi/Hrta2	(i) Mitochondrial location; (ii) Interaction with PINK1	Loss of function mutations found in PD patients
LRRK2	(i) Protects against mitochondrial CI toxin rotenone; (ii) Increases Parkin mediated cell protection; (iii) Located in outer mitochondrial membrane	Mutation linked with autosomal dominant PD
ATP13A2	Leads to lysosomal dysfunction and build up of α-synuclein which is toxic to CI	Mutation linked with hereditary form of PD
PLA2G6	(i) Located in mitochondria; (ii) Protect mitochondria against oxidative stress	Mutations linked to neurodegeneration and recently PD
TFAM	(i) Regulates transcription of mtDNA; (ii) Knockout mouse has respiratory chain deficiency	(i) Knockout mouse develops PD phenotype; (ii) Mutations in some variants give increased risk of PD
POLG1	(i) Involved in the synthesis and regulation of mtDNA; (ii) Linked to respiratory chain deficiency in PD	Mutation linked with PD