SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma.
SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma.
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DOI：
10.1126/science.1175689
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发表时间：
2009-08-28
期刊：
影响因子：
--
通讯作者：
Rutter J
中科院分区：
文献类型：
--
作者：
Hao HX;Khalimonchuk O;Schraders M;Dephoure N;Bayley JP;Kunst H;Devilee P;Cremers CW;Schiffman JD;Bentz BG;Gygi SP;Winge DR;Kremer H;Rutter J
哺乳动物的线粒体含有大约1100种蛋白质，其中近300种是未被鉴定的。鉴于线粒体缺陷在人类疾病中的作用，这些蛋白质的功能表征可能为疾病机制提供新的线索。从酵母作为模型系统开始，我们研究了一种未表征但高度保守的线粒体蛋白（这里命名为Sdh5）。酵母和人的sd5都与琥珀酸脱氢酶（SDH）复合物的催化亚基相互作用，SDH是电子传递链和三羧酸循环的组成部分。sdh依赖性呼吸和Sdh1黄化（黄素腺嘌呤二核苷酸辅因子的结合）需要Sdh5。位于染色体11q13.1上的人类SDH5基因的种系功能丧失突变与遗传性副神经节瘤家族的疾病分离。副神经节瘤是一种神经内分泌肿瘤，以前与编码SDH亚基的基因突变有关。因此，酵母的线粒体蛋白质组学分析导致了人类肿瘤易感基因的发现。
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.
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影响因子：
4.8
作者：
Bafunno, V;Giancaspero, TA;Barile, M
通讯作者：
Barile, M
影响因子：
3.2
作者：
Romano, JD;Kolter, R
通讯作者：
Kolter, R
DOI：
10.1093/jnci/djn254
发表时间：
2008-09-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Ricketts, Christopher;Woodward, Emma R.;Maher, Eamonn R.
通讯作者：
Maher, Eamonn R.
影响因子：
64.5
作者：
Pagliarini DJ;Calvo SE;Chang B;Sheth SA;Vafai SB;Ong SE;Walford GA;Sugiana C;Boneh A;Chen WK;Hill DE;Vidal M;Evans JG;Thorburn DR;Carr SA;Mootha VK
通讯作者：
Mootha VK
影响因子：
11.4
作者：
DUMONT, ME;ERNST, JF;SHERMAN, F
通讯作者：
SHERMAN, F