Modeling succinate dehydrogenase loss disorders in C. elegans through effects on hypoxia-inducible factor.

Autor: Megan M Braun, Tamara Damjanac, Yuxia Zhang, Chuan Chen, Jinghua Hu, L James Maher
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS ONE, Vol 14, Iss 12, p e0227033 (2019)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0227033
Popis: Mitochondrial disorders arise from defects in nuclear genes encoding enzymes of oxidative metabolism. Mutations of metabolic enzymes in somatic tissues can cause cancers due to oncometabolite accumulation. Paraganglioma and pheochromocytoma are examples, whose etiology and therapy are complicated by the absence of representative cell lines or animal models. These tumors can be driven by loss of the tricarboxylic acid cycle enzyme succinate dehydrogenase. We exploit the relationship between succinate accumulation, hypoxic signaling, egg-laying behavior, and morphology in C. elegans to create genetic and pharmacological models of succinate dehydrogenase loss disorders. With optimization, these models may enable future high-throughput screening efforts.
Databáze: Directory of Open Access Journals
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