Vulnerable Parkin Loss-of-Function Drosophila Dopaminergic Neurons Have Advanced Mitochondrial Aging, Mitochondrial Network Loss and Transiently Reduced Autophagosome Recruitment

Frontiers in Cellular Neuroscience
Juliana CackovicLori M Buhlman

Abstract

Selective degeneration of substantia nigra dopaminergic (DA) neurons is a hallmark pathology of familial Parkinson's disease (PD). While the mechanism of degeneration is elusive, abnormalities in mitochondrial function and turnover are strongly implicated. An Autosomal Recessive-Juvenile Parkinsonism (AR-JP) Drosophila melanogaster model exhibits DA neurodegeneration as well as aberrant mitochondrial dynamics and function. Disruptions in mitophagy have been observed in parkin loss-of-function models, and changes in mitochondrial respiration have been reported in patient fibroblasts. Whether loss of parkin causes selective DA neurodegeneration in vivo as a result of lost or decreased mitophagy is unknown. This study employs the use of fluorescent constructs expressed in Drosophila DA neurons that are functionally homologous to those of the mammalian substantia nigra. We provide evidence that degenerating DA neurons in parkin loss-of-function mutant flies have advanced mitochondrial aging, and that mitochondrial networks are fragmented and contain swollen organelles. We also found that mitophagy initiation is decreased in park (Drosophila parkin/PARK2 ortholog) homozygous mutants, but autophagosome formation is unaffected, and mi...Continue Reading

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Citations

Dec 20, 2018·International Journal of Molecular Sciences·Federica De LazzariFederica Sandrelli
Jan 21, 2021·Translational Neurodegeneration·Iryna KamienievaJoanna Szczepanowska
Feb 7, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Nicholas SchultheisScott B Selleck
Aug 24, 2021·Frontiers in Aging Neuroscience·Maria Shadrina, Petr Slominsky
Sep 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lori M BuhlmanTheresa Currier Thomas

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Methods Mentioned

BETA
ubiquitination
PCR
GTPase

Software Mentioned

Excel
Image Studio
Image Pro Premier

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