Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models

Cell Death & Disease
Hanna KimKim A Caldwell

Abstract

Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respec...Continue Reading

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Citations

Mar 7, 2019·Cellular and Molecular Life Sciences : CMLS·Joseph J ByrneBrent Neumann
Apr 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kelly H OhHongkyun Kim
Oct 30, 2019·The FEBS Journal·Corina T Madreiter-SokolowskiWolfgang F Graier
Jul 6, 2021·Cardiovascular Therapeutics·Mingqi OuyangBilian Yu

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Methods Mentioned

BETA
GTPases
column chromatography
transgenic
PCR
electrophoresis

Software Mentioned

GraphPad Prism
MetaMorph

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