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


Autoři: Megan M. Braun aff001;  Tamara Damjanac aff001;  Yuxia Zhang aff001;  Chuan Chen aff001;  Jinghua Hu aff001;  L. James Maher, III aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227033

Souhrn

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.

Klíčová slova:

Caenorhabditis elegans – Drug metabolism – Enzyme metabolism – Enzymes – Library screening – Phenotypes – RNA interference – Sequence assembly tools


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2019 Číslo 12