Journal
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
Volume 41, Issue 6, Pages 481-486Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10863-009-9256-0
Keywords
PINK1; Parkin; Mitochondria; Oxidative stress; Parkinson's disease
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Funding
- BMBF [01GS08138]
- DFG [AU96/10-2, GI 342/3-1]
- Parkinson Initiative and the Mitochondrial Research Consortium at the Klinikum Goethe Universitat Frankfurt
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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.
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