The mitochondrial kinase PINK1, stress response and Parkinson's disease.

Journal of Bioenergetics and Biomembranes
Marina JendrachGeorg Auburger

Abstract

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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Citations

Oct 27, 2011·Neurogenetics·M KlinkenbergM Jendrach
Dec 30, 2009·Journal of Bioenergetics and Biomembranes·George H Sack
Feb 22, 2012·Molecular Neurobiology·Georg AuburgerMarina Jendrach
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Apr 23, 2014·PloS One·Dajana ParganlijaMarina Jendrach
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Sep 4, 2012·Progress in Neurobiology·Inês Marques-AleixoAntónio Ascensão
Jan 24, 2014·Metallomics : Integrated Biometal Science·Julia BornhorstMichael Aschner
Nov 12, 2017·Journal of Anesthesia·Chao LiangZhanggang Xue

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