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Modeling succinate dehydrogenase loss disorders in C. elegans through effects on hypoxia-inducible factor.
- Source :
-
PloS one [PLoS One] 2019 Dec 30; Vol. 14 (12), pp. e0227033. Date of Electronic Publication: 2019 Dec 30 (Print Publication: 2019). - Publication Year :
- 2019
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adrenal Gland Neoplasms drug therapy
Adrenal Gland Neoplasms pathology
Amino Acids, Dicarboxylic pharmacology
Animals
Animals, Genetically Modified
Caenorhabditis elegans genetics
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins antagonists & inhibitors
Caenorhabditis elegans Proteins metabolism
Cell Hypoxia drug effects
Cell Hypoxia genetics
Disease Models, Animal
Drug Screening Assays, Antitumor methods
High-Throughput Screening Assays methods
Humans
Mutation
Paraganglioma drug therapy
Paraganglioma pathology
Pheochromocytoma drug therapy
Pheochromocytoma pathology
Succinate Dehydrogenase antagonists & inhibitors
Succinate Dehydrogenase metabolism
Succinic Acid metabolism
Adrenal Gland Neoplasms genetics
Caenorhabditis elegans Proteins genetics
Paraganglioma genetics
Pheochromocytoma genetics
Succinate Dehydrogenase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31887185
- Full Text :
- https://doi.org/10.1371/journal.pone.0227033