The role of mitochondrial calcium in PINK1/Parkin related Parkinson's disease
Alex Whitworth  1  
1 : MRC Mitochondrial Biology Unit, Cambridge

Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson's disease (PD). Loss of function mutations in parkin and PINK1 cause the majority of early onset PD which can be elegantly modelled in Drosophila. Genetic studies in Drosophila established that PINK1 and Parkin act in a common pathway to maintain mitochondrial homeostasis, and impinge on the mitochondrial fission/fusion machinery. Substantial in vitro evidence has implicated PINK1-Parkin in regulating mitochondrial autophagy (mitophagy), however, the in vivo relevance and cause of cell death remains unclear. We have recently generated mitophagy reporter lines with show a surprising lack of impact of PINK1/Parkin on basal mitophagy raising questions about the physiological regulation of mitophagy. Considering a potential pathogenic cause we assessed the impact of mitochondrial calcium overload. Generating new mutants in the mitochondrial calcium uniporter (MCU) complex components we found that limiting mitochondrial calcium uptake can prevent some of the Pink1/parkin phenotypes. These findings support calcium overload as a contributing factor in PINK1/Parkin pathogenesis.


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