SDH5, a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma.

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Bibliographic Details
Title:	SDH5, a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma.
Authors:	Huai-Xiang Hao, Khalimonchuk, Oleh, Schraders, Margit, Dephoure, Noah, Bayley, Jean-Pierre, Kunst, Henricus, Devilee, Peter, Cremers, Cor W. R. J., Schiffman, Joshua D., Bentz, Brandon G., Gygi, Steven P., Winge, Dennis R., Kremer, Hannie, Rutter, Jared
Source:	Science (pre-March 2025). 8/28/2009, Vol. 325 Issue 5944, p1139-1142. 4p.
Subjects:	Succinate dehydrogenase, Paraganglioma, Genetic mutation, Mitochondria, Protein research, Yeast research, Krebs cycle, Proteomics
Abstract:	Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new tight on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits. Thus, a mitochondrial proteomics analysis in yeast has led to the discovery of a human tumor susceptibility gene. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new tight on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits. Thus, a mitochondrial proteomics analysis in yeast has led to the discovery of a human tumor susceptibility gene. [ABSTRACT FROM AUTHOR]
ISSN:	00368075
DOI:	10.1126/science.1175689