TY  - JOUR
A1  - Jendrach, Marina
A1  - Gispert, Suzana
A1  - Ricciardi, Filomena
A1  - Klinkenberg, Michael
A1  - Schemm, Rudolf
A1  - Auburger, Georg
T1  - The mitochondrial kinase PINK1, stress response and Parkinson's disease
T2  - Journal of Bioenergetics and Biomembranes
N2  - Mitochondrial dysfunction is well documented in presymptomatic brain tissue with Parkinson's disease (PD). Identification of the autosomal recessive variant PARK6 caused by loss-of-function mutations in the mitochondrial kinase PINK1 provides an opportunity to dissect pathogenesis. Although PARK6 shows clinical differences to PD, the induction of alpha-synuclein "Lewy" pathology by PINK1-deficiency proves that mitochondrial pathomechanisms are relevant for old-age PD. Mitochondrial dysfunction is induced by PINK1 deficiency even in peripheral tissues unaffected by disease, consistent with the ubiquitous expression of PINK1. It remains unclear whether this dysfunction is due to PINK1-mediated phosphorylation of proteins inside or outside mitochondria. Although PINK1 deficiency affects the mitochondrial fission/fusion balance, cell stress is required in mammals to alter mitochondrial dynamics and provoke apoptosis. Clearance of damaged mitochondria depends on pathways including PINK1 and Parkin and is critical for postmitotic neurons with high energy demand and cumulative stress, providing a mechanistic concept for the tissue specificity of disease.
KW  - PINK1
KW  - Parkin
KW  - Mitochondria
KW  - Oxidative stress
KW  - Parkinson’s disease
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33420
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-334200
SN  - 0145-479X
SN  - 1573-6881
VL  - 41
IS  - 6
SP  - 481
EP  - 486
PB  - Springer
CY  - Dordrecht
ER  -