Dysregulated iron metabolism in C. elegans catp-6/ATP13A2 mutant impairs mitochondrial function.

Dysregulated iron metabolism in C. elegans catp-6/ATP13A2 mutant impairs mitochondrial function. Neurobiol Dis. 2020 Feb 04;:104786 Authors: Anand N, Holcom A, Broussalian M, Schmidt M, Chinta SJ, Lithgow GJ, Andersen JK, Chamoli M Abstract Mutations in the human ATP13A2 gene are associated with an early-onset form of Parkinson's disease (PD) known as Kufor Rakeb Syndrome (KRS). Patients with KRS show increased iron deposition in the basal ganglia, suggesting iron toxicity-induced neurodegeneration as a potential pathogenesis associated with the ATP13A2 mutation. Previously we demonstrated that functional losses of ATP13A2 disrupt the lysosome's ability to store excess iron, leading to reduce survival of dopaminergic neuronal cells. To understand the possible mechanisms involved, we studied a Caenorhabditis elegans mutant defective in catp-6 function, an ortholog of human ATP13A2 gene. Here we show that catp-6 mutant worms have defective autophagy and lysosomal function, demonstrate characteristic PD phenotypes including reduced motor function and dysregulated iron metabolism. Additionally, these mutants have defective mitochondrial health, which is rescuable via iron chelation or mitophagy induction. PMID: 32032734 [PubMed - as supplied by publisher]
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research