PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency.

Molecular Neurodegeneration
Sheila K PiroozniaTed M Dawson

Abstract

Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing PINK1 and parkin in common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent mitochondrial pathways to dopamine neuron degeneration in PD is lacking. Although PINK1 and parkin are known to regulate mitophagy, emerging data suggest that defects in mitophagy are unlikely to be of pathological relevance. Mitochondrial functions of PINK1 and parkin are also tied to their proteasomal regulation of specific substrates. In this study, we examined how PINK1/parkin mediated regulation of the pathogenic substrate PARIS impacts dopaminergic mitochondrial network homeostasis and neuronal survival in Drosophila. The UAS-Gal4 system was employed for cell-type specific expression of the various transgenes. Effects on dopamine neuronal survival and function were assessed by anti-TH immunostaining and negative geotaxis assays. Mitochondrial effects were probed by quantitative analysis of mito-GFP labeled dopaminergic mitochondria, assessment of mitochondrial abundance in dopamine neurons isolated by Fluorescence Activated Cell Sortin...Continue Reading

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Citations

Oct 20, 2020·Journal of Parkinson's Disease·Max BorscheAnne Grünewald
Dec 30, 2020·The Journal of Biological Chemistry·Emily H ClarkThomas Briston
Feb 7, 2021·International Journal of Molecular Sciences·Chunling HuangCarol A Pollock
Jan 8, 2021·The Journal of Biological Chemistry·Emily H ClarkThomas Briston
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Apr 4, 2021·International Journal of Molecular Sciences·Elena PiccininGaetano Villani
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Aug 28, 2021·Frontiers in Cell and Developmental Biology·Jiahui TangYiqing Li
Oct 8, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Liam PollockMichael J Clague

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Methods Mentioned

BETA
electron microscopy
transgenic
Fluorescence Activated Cell Sorting
transfection
PCR
dissection
protein assay
co-immunoprecipitation
pull down
FACS

Software Mentioned

Graphpad Prism
GraphPad
ImageJ

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