Publication Date:
2009-07-25
Description:
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 light 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hao, Huai-Xiang -- 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 -- DK071962/DK/NIDDK NIH HHS/ -- GM087346/GM/NIGMS NIH HHS/ -- R01 ES003817/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 28;325(5944):1139-42. doi: 10.1126/science.1175689. Epub 2009 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628817" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Cell Line
;
Cell Line, Tumor
;
Female
;
Flavin-Adenine Dinucleotide/metabolism
;
Flavoproteins/metabolism
;
*Germ-Line Mutation
;
Haplotypes
;
Humans
;
Inheritance Patterns
;
Male
;
Mitochondria/*metabolism
;
Mitochondrial Proteins/chemistry/*genetics/metabolism
;
Molecular Sequence Data
;
Oxygen Consumption
;
Paraganglioma/*genetics
;
Pedigree
;
Protein Subunits/metabolism
;
Proteomics
;
Saccharomyces cerevisiae/*genetics/growth & development/metabolism
;
Saccharomyces cerevisiae Proteins/chemistry/*genetics/*metabolism
;
Succinate Dehydrogenase/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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