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

Megan M. Braun, Tamara Damjanac, Yuxia Zhang, Chuan Chen, Jinghua Hu, L. James Maher

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0227033
JournalPloS one
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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