Complex I superoxide anion production is necessary and sufficient for complex I inhibitor-induced dopaminergic neurodegeneration in Caenorhabditis elegans.

ABSTRACT: Parkinson's Disease (PD) is the 2^nd most prevalent neurodegenerative disease, but there is currently no cure and limited understanding of the pathogenesis resulting in dopaminergic neurodegeneration. Inhibitors of electron transport chain Complex I (CI) have long been associated with and are now used to model PD, but CI inhibition results in multiple effects including ATP depletion and reactive oxygen species (ROS) generation. The lack of tools to isolate effects of CI inhibition have rendered it difficult to determine which mechanistic step is critical for CI inhibitor-induced dopaminergic neurodegeneration. Here we report that CI-derived superoxide anion, not ATP depletion, is the critical driver of CI inhibitor-induced dopaminergic neurodegeneration in the model organism Caen

SUBMITTER: Morton KS 

PROVIDER: S-EPMC11875150 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature