The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
SDH5 , a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma
Open accessAbstract
Tapping the Mitochondrial Proteome: Mitochondria produce the energy that cells need to survive, function, and divide. A growing list of human disorders has been traced to defects in mitochondrial function. About 300 mammalian mitochondrial proteins are functionally uncharacterized, and Hao et al. (p. 1139 , published online 23 July) reasoned that the most highly conserved proteins within this group might provide insights into human disease. A combination of bioinformatics, yeast genetics, biochemistry, and human genetics was used to show that a previously uncharacterized mitochondrial protein (Sdh5) is required for the activity of respiratory complex II. Inactivating mutations in the human gene encoding SDH5 were found in individuals with hereditary paraganglioma, a rare neuroendocrine tumor. Thus, analysis of a mitochondrial protein in yeast has revealed a human tumor susceptibility gene.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Despite ubiquitous expression of the metabolic enzyme succinate dehydrogenase (SDH), germline mutations in subunits of this complex cause cancer only in a few sites, including neuroendocrine tissues (paraganglioma), the adrenal gland (pheochromocytoma), and the stomach and small intestine (gastrointestinal stromal tumors) (8–10).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [10]
In the citing paper
“Germline SDH mutations have been identified in the SDH subunits SDHA–SDHD and also in SDH assembly factor 2 in tumor predisposition syndromes (Hao et al., 2009; Korpershoek et al., 2011; Neumann et al., 2004; Niemann and Müller, 2000; Oudijk et al., 2013; Pollard et al., 2005; Ricketts et al., 2008; Ricketts et al., 2010).”
From SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways (2013) · cites this paper as Hao et al., 2009
In the citing paper
“Consistently, heterozygous germline mutations in genes encoding the TCA cycle enzymes involved in the breakdown of these metabolites—SDH and FH—have been shown to facilitate the pathogenesis of certain rare cancers (e.g., paragangliomas) and inherited cancer-predisposition syndromes (181, 182, 183).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [182]
In the citing paper
“Loss-of-function mutations have been identified in all four subunits of the SDH complex (Baysal, 2008; Burnichon et al., 2010), and in SDH5, which encodes a protein involved in incorporation of SDH’s flavin adenine dinucleotide cofactor (Hao et al., 2009).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Hao et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994
The genome sequence of Rickettsia prowazekii and the origin of mitochondria
Andersson, S. G. E., Zomorodipour, A., Andersson, J. O., Sicheritz-Pontén, T., Alsmark, U. C. M., Podowski, R. M., Näslund, A. K., Eriksson, A.-S., Winkler, H. H., & Kurland, C. G. (1998) · Nature · doi:10.1038/24094 · Cited by 1,697
The proteome of Saccharomyces cerevisiae mitochondria
Sickmann, A., Reinders, J., Wagner, Y., Joppich, C., Zahedi, R. P., Meyer, H. E., Schönfisch, B., Perschil, I., Chacińska, A., Guiard, B., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135385100 · Cited by 895
Crystal Structure of Mitochondrial Respiratory Membrane Protein Complex II
Sun, F., Huo, X., Zhai, Y., Wang, A., Xu, J., Su, D., Bartlam, M., & Rao, Z. (2005) · Cell · doi:10.1016/j.cell.2005.05.025 · Cited by 881
Germline SDHB Mutations and Familial Renal Cell Carcinoma
Ricketts, C. J., Woodward, E. R., Killick, P., Morris, M. R., Astuti, D., Latif, F., & Maher, E. R. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn254 · Cited by 354
Baysal, B. E., Willett-Brozick, J. E., Lawrence, E. C., Drovdlic, C. M., Savul, S. A., McLeod, D. R., Yee, H. A., Brackmann, D. E., Slattery, W. H., Myers, E. N., et al. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.3.178 · Cited by 336
Predictors and Prevalence of Paraganglioma Syndrome Associated With Mutations of the SDHC Gene
Schiavi, F. (2005) · JAMA · doi:10.1001/jama.294.16.2057 · Cited by 332
Dumont, M. E., Ernst, J. F., Hampsey, D. M., & Sherman, F. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb04744.x · Cited by 228
Research works printed but not linked: 1
- Ghezzi D., et al.., Nat. Genet., 24 May 2009 (e-pub ahead of print).
Cited by
Sorted by citations
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427
“Mutations in SDH5, which is involved in the assembly of SDHD into the complex, were also recently documented in hereditary paraganglioma”
BackgroundMitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813
Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline
Lenders, J. W. M., Duh, Q.-Y., Eisenhofer, G., Gimenez-Roqueplo, A.-P., Grebe, S. K. G., Murad, M. H., Naruse, M., Pacak, K., & Young, W. F. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1498 · Cited by 2,827
Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740
“1016/S0002-9440(10)65628-3; pmid: 9736035”
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328
NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors
Demetri, G. D., von Mehren, M., Antonescu, C. R., DeMatteo, R. P., Ganjoo, K. N., Maki, R. G., Pisters, P. W. T., Raut, C. P., Riedel, R. F., Schuetze, S. M., et al. (2010) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2010.0116 · Cited by 1,215
Xiao, M., Yang, H., Xu, W., Ma, S., Lin, H., Zhu, H., Liu, L., Liu, Y., Yang, C., Xu, Y., et al. (2012) · Genes & Development · doi:10.1101/gad.191056.112 · Cited by 1,188
“Besides IDH1 and IDH2, six genes (FH, SDHA, SDHB, SDHC, SDHD, and SDHAF2), encoding for the subunits of two different Krebs cycle enzymes (FH and SDH), are mutated both germinally and somatically in a number of human cancers (Hao et al. 2009; Kaelin 2009; Baysal et al. 2000; Astuti et al. 2001; Bayley et al. 2010; Oer…”
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.001 · Cited by 1,000
“…SDH. Germline SDH mutations have been identified in the SDH subunits SDHA– SDHD and also in SDH assembly factor 2 in tumor predisposition syndromes (Hao et al., 2009; Korpershoek et al., 2011; Neumann et al., 2004; Niemann and Müller, 2000; Oudijk et al., 2013; Pollard et al., 2005; Ricketts et…”
BackgroundCellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
DeBerardinis, R. J., & Thompson, C. B. (2012) · Cell · doi:10.1016/j.cell.2012.02.032 · Cited by 858
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 818
“Fumarate and succinate antagonize the roles of α-KG In addition to IDH1 and IDH2, germinal and somatic mutations of fumarate hydratase (FH) and succinate dehydrogenases (SDHA, SDHB, SDHC, SDHD, and SDHAF2), encoding FH and SDH enzymes, are common in a number of human cancers (Baysal et al., 2000; Astuti et al., 2001;…”
BackgroundPheochromocytoma and Paraganglioma
Neumann, H. P. H., Young, W. F., & Eng, C. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1806651 · Cited by 736
Seyfried, T. N., & Shelton, L. M. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-7 · Cited by 675
“For example, risk for paraganglioma involves mutations in the succinate dehydrogenase gene, whereas risk for leiomyomatosis and renal cell carcinoma involves mutations in the fumarate hydratase (fumarase) gene [94-97].”
BackgroundSDHA is a tumor suppressor gene causing paraganglioma
Burnichon, N., Brière, J.-J., Libé, R., Vescovo, L., Rivière, J., Tissier, F., Jouanno, E., Jeunemaı̂tre, X., Bénit, P., Tzagoloff, A., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq206 · Cited by 645
“The requirement of SDHAF2 for flavination is supported by a dramatic decrease in FAD in SDHA with a concomitant loss of SDH enzymatic activity in SDHAF2-related paragangliomas (2).”
BackgroundInfluentialRealizing the promise of cancer predisposition genes
Rahman, N. (2014) · Nature · doi:10.1038/nature12981 · Cited by 632
Janeway, K. A., Kim, S. Y., Lodish, M., Nosé, V., Rustin, P., Gaal, J., Dahia, P. L. M., Liegl, B., Ball, E. R., Raygada, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009199108 · Cited by 628
The emerging role and targetability of the TCA cycle in cancer metabolism
Anderson, N. M., Mucka, P., Kern, J. G., & Feng, H. (2017) · Protein & Cell · doi:10.1007/s13238-017-0451-1 · Cited by 586
“Mutations in SDHA, SDHB, SDHC, SDHD and SDH assembly factor 2 (SDHAF2) have been identified in hereditary paragangliomas (hPGLs) and pheochromocytomas (PCCs) (Table 1) (Baysal et al., 2000; Niemann and Muller, 2000; Astuti et al., 2001; Baysal et al., 2002; Hao et al., 2009; Bayley et al., 2010; Burnichon et al., 2010…”
BackgroundSuccinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis
Tretter, L., Patócs, A., & Chinopoulos, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.012 · Cited by 550
Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
Comino‐Méndez, I., Gracia-Aznárez, F. J., Schiavi, F., Landa, I., Leandro-Garcia, L. J., Letón, R., Honrado, E., Ramos‐Medina, R., Caronia, D., Pita, G., et al. (2011) · Nature Genetics · doi:10.1038/ng.861 · Cited by 528
“861" language="eng" relation="no"> Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to dat”
BackgroundRegulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535
Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes
Etchegaray, J., & Mostoslavsky, R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.029 · Cited by 546
“…versions of the fumarate and succinate oxidizing enzymes FH and SDH, found in various human cancers (Baysal et al., 2000; Astuti et al., 2001; Hao et al., 2009; Kaelin 2009; Bayley et al., 2010; Oermann et al., 2012), cause genome-wide inhibition of H3K4 and H3K9 demethylation and…”
BackgroundParaganglioma and phaeochromocytoma: from genetics to personalized medicine
Favier, J., Amar, L., & Gimenez‐Roqueplo, A. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.188 · Cited by 484
Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity
Dahia, P. L. M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3648 · Cited by 545
Succinate dehydrogenase – Assembly, regulation and role in human disease
Rutter, J. P., Winge, D. R., & Schiffman, J. D. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.03.001 · Cited by 459
“In fact, yeast lacking one of the membrane anchor subunits shows a marked decrease in abundance of both of the hydrophilic subunits, Sdh1 and Sdh2 (Hao et al., 2009).”
BackgroundInfluentialSelf-citationAyala‐Ramirez, M., Feng, L., Johnson, M. M., Ejaz, S., Habra, M. A., Rich, T. A., Busaidy, N. L., Cote, G. J., Perrier, N. D., Phan, A. T., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1946 · Cited by 429
“SDHAF2 (PGL syndrome type 2) (11, 12), the SDHA, and”
BackgroundBardella, C., Pollard, P. J., & Tomlinson, I. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2011.07.003 · Cited by 395
Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas
Welander, J., Söderkvist, P., & Gimm, O. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0170 · Cited by 356
“The syndrome can be divided into PGL1, PGL2, PGL3, and PGL4, which are caused by mutations in SDHD, SDHAF2, SDHC, and SDHB respectively.”
BackgroundInfluentialMAX Mutations Cause Hereditary and Sporadic Pheochromocytoma and Paraganglioma
Burnichon, N., Cascón, A., Schiavi, F., Morales, N. P., Comino‐Méndez, I., Abermil, N., Inglada‐Pérez, L., de Cubas, A. A., Amar, L., Barontini, M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0160 · Cited by 331
“MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; 25Endocrinology Unit, Azienda Ospedaliera Universitaria Careggi; 26Department of Clinical Pathophysiology, University of Florence; 27Istituto Toscano Tumori, Florence, Italy; 28Endocrinology Unit, Centre Hospitalier de Rennes, Rennes, France; 29Anato…”
BackgroundInfluentialMetabolic reprogramming and epithelial‐to‐mesenchymal transition in cancer
Sciacovelli, M., & Frezza, C. (2017) · FEBS Journal · doi:10.1111/febs.14090 · Cited by 334
New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification
Crona, J., Taïeb, D., & Pacák, K. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00062 · Cited by 330
Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes
Laukka, T., Mariani, C. J., Ihantola, T., Cao, J. Z., Hokkanen, J., Kaelin, W. G., Godley, L. A., & Koivunen, P. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.688762 · Cited by 307
A Stress-Responsive System for Mitochondrial Protein Degradation
Heo, J.-M., Livnat-Levanon, N., Taylor, E. B., Jones, K. T., Dephoure, N., Ring, J., Xie, J., Brodsky, J. L., Madeo, F., Gygi, S. P., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.021 · Cited by 304
“By virtue of this observation, we identified the human SDH5 ortholog as the causative gene in a familial form of the paraganglioma neuroendocrine tumor syndrome (Hao et al., 2009).”
BackgroundSelf-citationMitochondrial disorders of the OXPHOS system
Fernández‐Vizarra, E., & Zeviani, M. (2020) · FEBS Letters · doi:10.1002/1873-3468.13995 · Cited by 323
Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma
Burnichon, N., Vescovo, L., Amar, L., Libé, R., de Reyniès, A., Vénisse, A., Jouanno, E., Laurendeau, I., Parfait, B., Bertherat, J. Y., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr324 · Cited by 304
Role of mitochondrial dysfunction in cancer progression
Hsu, C., Tseng, L., & Lee, H. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216641787 · Cited by 320
“The four subunits are encoded by nuclear genes and two assembly factors, SDH assembly factor 1 (SDHAF1) and SDHAF2, are essential for the assembly and activity of the SDH protein complex.(69,70) In the TCA cycle, the SDH complex converts succinate into fumarate in a reaction that is coupled to the reduction of flavin…”
BackgroundMitochondrial complex ii: At the crossroads
Bezawork-Geleta, A., Rohlena, J., Dong, L., Pacak, K., & Neuzil, J. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.01.003 · Cited by 295
“In the mitochondrial matrix, SDHA was proposed to be flavinated by the SDHAF2 (SDH5) protein (Sdh5 in yeast), and SDHAF2 is required for the covalent attachment of FAD to the catalytic SDHA (Sdh1 in yeast) subunit; the G78R mutation in SDHAF2 is associated with PGL [36].”
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 301
Bardella, C., El‐Bahrawy, M., Frizzell, N., Adam, J., Ternette, N., Hatipoglu, E., Howarth, K., O'Flaherty, L., Roberts, I., Turner, G., et al. (2011) · The Journal of Pathology · doi:10.1002/path.2932 · Cited by 281
Assembly of mammalian oxidative phosphorylation complexes I–V and supercomplexes
Signes, A., & Fernandez-Vizarra, E. (2018) · Essays in Biochemistry · doi:10.1042/ebc20170098 · Cited by 267
Korpershoek, E., Favier, J., Gaal, J., Burnichon, N., van Gessel, B., Oudijk, L., Badoual, C., Gadessaud, N., Venisse, A., Bayley, J.-P., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1043 · Cited by 277
Self-citationGill, A. J., Benn, D. E., Chou, A. S. Y., Clarkson, A., Muljono, A., Meyer-Rochow, G. Y., Richardson, A. L., Sidhu, S. B., Robinson, B. G., & Clifton-Bligh, R. J. (2010) · Human Pathology · doi:10.1016/j.humpath.2009.12.005 · Cited by 281
SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma
Bayley, J., Kunst, H. P. M., Cascón, A., Sampietro, M. L., Gaal, J., Korpershoek, E., Hinojar‐Gutiérrez, A., Timmers, H. J. L. M., Hoefsloot, L. H., Hermsen, M. A. J. A., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70007-3 · Cited by 283
Self-citationRevisiting the TCA cycle: signaling to tumor formation
Raimundo, N., Baysal, B. E., & Shadel, G. S. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.06.001 · Cited by 281
“More recently, dominant defects in SDH5 were also found to predispose individuals to paragangliomas [13].”
BackgroundInterplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches
Wong, C. C., Qian, Y., & Yu, J. Q. (2017) · Oncogene · doi:10.1038/onc.2016.485 · Cited by 266
The impact of rare variation on gene expression across tissues
Li, X., Kim, Y., Tsang, E. K., Davis, J. R., Damani, F. N., Chiang, C., Hess, G. T., Zappala, Z., Strober, B. J., Scott, A. J., et al. (2017) · Nature · doi:10.1038/nature24267 · Cited by 253
Mitochondrial Homeostasis and Cellular Senescence
Vasileiou, P. V. S., Evangelou, K., Vlasis, K. G., Fildisis, G., Panayiotidis, M. I., Chronopoulos, E., Passias, P.-G., Kouloukoussa, M., Gorgoulis, V. G., & Havaki, S. (2019) · Cells · doi:10.3390/cells8070686 · Cited by 255
Fishbein, L. M., Merrill, S. L., Fraker, D. L., Cohen, D. L., & Nathanson, K. L. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-013-2942-5 · Cited by 242
Palma, F. R., He, C., Danes, J. M., Paviani, V., Coelho, D. R., Gantner, B. N., & Bonini, M. G. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7962 · Cited by 253
“This kind of dysfunction in the Kreb’s cycle is now known to provoke changes to cellular metabolism (93, 106, 136) that have historically been associated with malignant transformation and carcinogenesis (26, 51, 108, 116).”
BackgroundWaguespack, S. G., Rich, T. A., Grubbs, E. G., Ying, A. K., Perrier, N. D., Ayala‐Ramirez, M., & Jiménez, C. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2830 · Cited by 229
Lussey-Lepoutre, C., Hollinshead, K. E. R., Ludwig, C., Menara, M., Morin, A., Castro-Vega, L.-J., Parker, S. J., Janin, M., Martinelli, C., Ottolenghi, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms9784 · Cited by 227
“Carbon from glutamine was significantly enriched in both aspartate and malate in positions consistent with oxidative TCA cycle activity in WT imCC ( 13 C 4 , 13 C-[1,2] and 13 C-[3,4]-malate and aspartate; Fig.”
InfluentialSuccinate dehydrogenase: the complex roles of a simple enzyme
Huang, S., & Millar, A. H. (2013) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2013.02.007 · Cited by 226
“Two assembly factors for SDH, SDHAF1 and SDHAF2 (Figure 1), were recently reported in mammals as the cause of different human diseases [12,13].”
BackgroundMitochondrial Structure and Bioenergetics in Normal and Disease Conditions
Protasoni, M., & Zeviani, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020586 · Cited by 243
“SDHA is initially imported into the matrix as an apo-protein and the FAD cofactor is inserted thanks to the interaction with the assembly factor SDHAF2/Sdh5 [183].”
BackgroundZdzisińska, B., Żurek, A., & Kandefer-Szerszeń, M. (2017) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-016-0406-x · Cited by 221
“SDH is a heterotetramer complex localised in mitochondria and composed of subunits A, B, C, and D and the SDH5 factor involved in tetramer mounting (Hao et al. 2009).”
BackgroundImmunohistochemistry for SDHB Divides Gastrointestinal Stromal Tumors (GISTs) into 2 Distinct Types
Gill, A. J., Chou, A. S. Y., Vilain, R. E., Clarkson, A., Lui, M., Jin, R., Tobias, V., Samra, J. S., Goldstein, D., Smith, C. J., et al. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181d6150d · Cited by 217
Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia
Gill, A. J. (2012) · Pathology · doi:10.1097/pat.0b013e3283539932 · Cited by 215
“It was only after these first reports that germline mutation of SDHAF2 (previously called SDH5) and SDHA were shown to be associated with PHEO/PGL.(18,19) The PHEO/PGL associated with these mutations have now been shown to also demonstrate negative staining for SDHB.”
BackgroundInfluentialChen, Y., Umanah, G. K. E., Dephoure, N., Andrabi, S. A., Gygi, S. P., Dawson, T. M., Dawson, V. L., & Rutter, J. P. (2014) · The EMBO Journal · doi:10.15252/embj.201487943 · Cited by 219
“As a result of our ongoing project to functionally annotate the mitochondrial proteome (Hao et al, 2009; Heo et al, 2010; Bricker et al, 2012; Chen et al, 2012), we here describe the previously unknown function of Ygr028 (or Msp1) in yeast and ATAD1 (also known as Thorase) in mammals, which are…”
BackgroundSelf-citationNeurocristopathies: New insights 150 years after the neural crest discovery
Vega‐López, G. A., Cerrizuela, S., Tríbulo, C., & Aybar, M. J. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.05.013 · Cited by 219
Tong, W.-H., Sourbier, C., Kovtunovych, G., Jeong, S. Y., Vira, M., Ghosh, M., Romero, V. V., Sougrat, R., Vaulont, S., Viollet, B., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.07.018 · Cited by 212
“, 2002), whereas germline mutations in SDH are associated with paragangliomas (PGL), pheochromocytomas (PHEO), and renal cell carcinoma (RCC) (Baysal et al., 2000; Hao et al., 2009).”
Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria
Thomas, L. W., & Ashcroft, M. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03039-y · Cited by 219
López-Jiménez, E. A., Goméz-López, G., Leandro-Garcia, L. J., Muñoz, I., Schiavi, F., Montero‐Conde, C., de Cubas, A. A., Fernández‐Ramires, R., Landa, I., Leskelä, S., et al. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0256 · Cited by 213
Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background
Fishbein, L. M., & Nathanson, K. L. (2012) · Cancer Genetics · doi:10.1016/j.cancergen.2012.01.009 · Cited by 206
“PGL2 (SDHAF2) The gene for PGL2 syndrome been identified as SDHAF2, also known as SDH5 (59).”
BackgroundInfluentialIdentification of a Protein Mediating Respiratory Supercomplex Stability
Chen, Y.-C., Taylor, E. B., Dephoure, N., Heo, J.-M., Tonhato, A., Papandreou, I., Nath, N., Denko, N. C., Gygi, S. P., & Rutter, J. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.006 · Cited by 205
“We previously described the function of SDH5/SDHAF2, which is required for assembly of ETC Complex II and is mutated in multiple families afflicted with the paraganglioma tumor syndrome (Bayley et al., 2010; Hao et al., 2009).”
BackgroundSelf-citationPheochromocytoma and paraganglioma: Diagnosis, genetics, management, and treatment
Martucci, V. L., & Pacák, K. (2014) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2014.01.001 · Cited by 212
Riboflavin transport and metabolism in humans
Barile, M., Giancaspero, T. A., Leone, P., Galluccio, M., & Indiveri, C. (2016) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-016-9950-0 · Cited by 205
“…and inserting in some human proteins of inorganic (Bonomi et al 2008; Ye and Rouault 2010; Leitch et al 2012; Rouault 2015) and organic cofactors (Padovani and Banerjee 2009), we propose that hFADS is a part of a Bflavinylation machinery^ previously named mtFSF (Brizio et al 2000; Hao et al 2009).”
Background15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1–5
Benn, D. E., Robinson, B. G., & Clifton-Bligh, R. J. (2015) · Endocrine Related Cancer · doi:10.1530/erc-15-0268 · Cited by 200
“SDHAF2, required for flavination of SDHA, is mutated in the rare PGL2 (Hao et al. 2009), and PGL5 is associated with mutations in SDHA (Burnichon et al.”
BackgroundInfluentialMitochondrial protein quality control during biogenesis and aging
Baker, B. M., & Haynes, C. M. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.01.004 · Cited by 195
King, K. S., Prodanov, T., Kantorovich, V., Fojo, T., Hewitt, J. K., Zacharin, M., WESLEY, R. A., Lodish, M. B., Raygada, M. J., Gimenez‐Roqueplo, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.6353 · Cited by 193
Whole-Exome Sequencing Identifies MDH2 as a New Familial Paraganglioma Gene
Cascón, A., Comino‐Méndez, I., Currás-Freixes, M., de Cubas, A. A., Contreras, L., Richter, S., Peitzsch, M., Mančíková, V., Inglada‐Pérez, L., Pérez‐Barrios, A., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv053 · Cited by 204
Renal Tumors Associated With Germline SDHB Mutation Show Distinctive Morphology
Gill, A. J., Pachter, N., Chou, A. S. Y., Young, B., Clarkson, A., Tucker, K., Winship, I., Earls, P., Benn, D. E., Robinson, B. G., et al. (2011) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e318227e7f4 · Cited by 186
“16,19 Mutations of SDHAF2 (formerly known as SDH5) may be the cause of PGL2.”
BackgroundMechanisms of mitochondrial diseases
Ylikallio, E., & Suomalainen, A. (2011) · Annals of Medicine · doi:10.3109/07853890.2011.598547 · Cited by 197
The assembly of succinate dehydrogenase: a key enzyme in bioenergetics
Moosavi, B., Berry, E. A., Zhu, X., Yang, W., & Yang, G. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03200-7 · Cited by 184
Robust succinic acid production from crude glycerol using engineered Yarrowia lipolytica
Gao, C., Yang, X., Wang, H., Pérez‐Rivero, C., Li, C., Cui, Z., Qi, Q., & Lin, C. S. K. (2016) · Biotechnology for Biofuels · doi:10.1186/s13068-016-0597-8 · Cited by 180
“The fifth subunit SDH5, a highly conserved mitochondrial protein in SDH complex, is required for SDH activity and stability [18].”
BackgroundPHGDH defines a metabolic subtype in lung adenocarcinomas with poor prognosis
Zhang, B., Zheng, A., Hydbring, P., Ambroise, G., Ouchida, A. T., Goiny, M., Vakifahmetoglu-Norberg, H., & Norberg, E. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.067 · Cited by 178
Oncometabolites: Unconventional triggers of oncogenic signalling cascades
Sciacovelli, M., & Frezza, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.025 · Cited by 184
“Mutations in SDH are found in familial paraganglioma and pheochromocytoma [14 – 17, 24 , 25 One of the most striking features of SDH-de fi cient cells is the accumulation of succinate [31], a metabolite implicated in tumorigenesis and, for this reasons, recently de fi ned an oncometa-bolite [32].”
BackgroundFrom complete genome sequence to ‘complete’ understanding?
Galperin, M. Y., & Koonin, E. V. (2010) · Trends in biotechnology · doi:10.1016/j.tibtech.2010.05.006 · Cited by 183
“In eukaryotes, products of some, albeit not all, of these widely conserved genes appear to be targeted to mitochondria [44–48].”
Metabolic changes in cancer: beyond the Warburg effect
Wu, W., & Zhao, S. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms104 · Cited by 173
Hypoxia-Inducible Factor Signaling in Pheochromocytoma: Turning the Rudder in the Right Direction
Jochmanová, I., Yang, C., Zhuang, Z., & Pacák, K. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt201 · Cited by 176
“The other known PHEO and PGL susceptibility genes include the SDH subunits—SDHA, SDHB, SDHC, and SDHD (74–77)—and succinate dehydrogenase complex assembly factor 2 (SDHAF2) (119).”
BackgroundCochaperone Binding to LYR Motifs Confers Specificity of Iron Sulfur Cluster Delivery
Maio, N., Singh, A., Uhrigshardt, H., Saxena, N., Tong, W.-H., & Rouault, T. A. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.015 · Cited by 167
“After resolution of mitochondrial extracts by BN-PAGE, three SDHB-containing complexes were identified (Figure 2B), including CII, which conformed to the predicted size of fully assembled complex II on BN-PAGE (220 KDa) (Hao et al., 2009), CIIa, which appeared to represent an assembly intermediate composed of SDHA and…”
InfluentialMitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases
Patergnani, S., Bouhamida, E., Leo, S., Pinton, P., & Rimessi, A. (2021) · Biomedicines · doi:10.3390/biomedicines9020216 · Cited by 178
TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State
Cardaci, S., & Ciriolo, M. R. (2012) · International Journal of Cell Biology · doi:10.1155/2012/161837 · Cited by 169
“More recently, mutations in SDHA and the SDH assembly factor 2 (SDHAF2), required for flavination of SDH [13, 14], have been associated with hPGL/PCC syndrome [15].”
BackgroundPhilip, B., Ito, K., Moreno‐Sánchez, R., & Ralph, S. J. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt209 · Cited by 166
“Hence, decreased 2-OG with increasing succinate (and/or citrate, fumarate, pyruvate, malate) levels will trigger HIF-1α activity, thereby leading to a state of pseudohypoxia (71,72).”
Mitochondrial complex II and reactive oxygen species in disease and therapy
Vanova, K. H., Kraus, M., Neužil, J., & Rohlena, J. (2020) · Redox Report · doi:10.1080/13510002.2020.1752002 · Cited by 166
“maturation of SDHA, and may facilitate covalent flavinylation [24,27,28].”
BackgroundMitochondrial Composition, Function and Stress Response in PlantsF
Jacoby, R. P., Li, L., Huang, S., Lee, C. P., Millar, A. H., & Taylor, N. L. (2012) · Journal of Integrative Plant Biology · doi:10.1111/j.1744-7909.2012.01177.x · Cited by 165
Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies
Lasserre, J.-P., Dautant, A., Aiyar, R. S., Kucharczyk, R., Glatigny, A., Tribouillard‐Tanvier, D., Rytka, J., Blondel, M., Skoczeń, N., Reynier, P., et al. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.020438 · Cited by 176
“Based on the causal relationship of loss of CII activity with a rare neuroendocrine tumor called paraganglioma (PGL), the human SDHAF2 gene was screened for mutations in such affected individuals.”
InfluentialComino-Méndez, I., de Cubas, A. A., Bernal, C., Álvarez-Escolá, C., Sánchez-Malo, C., Ramírez-Tortosa, C. L., Pedrinaci, S., Rapizzi, E., Ercolino, T., Bernini, G., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt069 · Cited by 169
Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
Lehtonen, H. J. (2011) · Familial Cancer · doi:10.1007/s10689-011-9428-z · Cited by 156
“Keywords Fumarate hydratase (FH) HIF1 HLRCC Kidney Leiomyoma Leiomyosarcoma MCUL Renal cell cancer Tricarboxylic acid cycle Abbreviations a-KG a-ketoglutarate CDC Collecting duct carcinoma CLM Cutaneous leiomyoma FH Fumarate hydratase FHD Fumarate hydratase deficiency FIH Factor inhibiting HIF HIF1 Hypoxia inducible f…”
BackgroundProtasoni, M., Pérez‐Pérez, R., Lobo‐Jarne, T., Harbour, M. E., Ding, S., Peñas, A., Díaz, F., Moraes, C. T., Fearnley, I. M., Zeviani, M., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019102817 · Cited by 152
“Conversely, the tenth cI assembly factor detected in this analysis, NDUFAF2 (Ogilvie et al , 2005), and the cII assembly factor SDHAF2 (Hao et al , 2009) were significantly more abundant in D 4-CYB mitochondria.”
Genetic insights into OXPHOS defect and its role in cancer
Chandra, D., & Singh, K. K. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.023 · Cited by 155
SDHAF2 (PGL2-SDH5) and Hereditary Head and Neck Paraganglioma
Kunst, H. P. M., Rutten, M., de Mönnink, J. P., Hoefsloot, L. H., Timmers, H. J. L. M., Marres, H. A. M., Jansen, J. C., Kremer, H., Bayley, J., & Cremers, C. W. R. J. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0420 · Cited by 151
“This gene, named SDHAF2 (succinate dehydrogenase complex assembly factor 2), encodes an evolutionarily highly conserved flavin-adenine dinucleotide factor (10).”
BackgroundSelf-citationPHGDH amplification and altered glucose metabolism in human melanoma
Mullarky, E., Mattaini, K. R., Heiden, M. G. V., Cantley, L. C., & Locasale, J. W. (2011) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2011.00919.x · Cited by 153
“Metabolic enzymes can play an important role in tumorigenesis, as evidenced by the predisposition of individuals with germline mutations in succinate dehydrogenase and fumarate hydratase to develop cancer (Hao et al., 2009; Pollard et al., 2003).”
BackgroundSomatic NF1 inactivation is a frequent event in sporadic pheochromocytoma
Burnichon, N., Buffet, A., Parfait, B., Letouzé, É., Laurendeau, I., Loriot, C., Pasmant, É., Abermil, N., Valeyrie‐Allanore, L., Bertherat, J. Y., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds374 · Cited by 159
“France, 7Assistance Publique-Hôpitaux de Paris, Hôpital Mondor, Centre de référence des Neurofibromatoses, Créteil F-94010, France, 8INSERM, U1016, CNRS UMR8104, Département d’Endocrinologie, Métabolisme & Cancer, Institut Cochin, Paris F-75014, France, 9Assistance Publique-Hôpitaux de Paris, Hôpital Cochin,…”
BackgroundAssembly Factors of Human Mitochondrial Respiratory Chain Complexes: Physiology and Pathophysiology
Ghezzi, D., & Zeviani, M. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_4 · Cited by 145
Cancer Genomics and Inherited Risk
Stadler, Z. K., Schrader, K. A., Vijai, J., Robson, M. E., & Offit, K. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.49.7271 · Cited by 149
Inborn and acquired metabolic defects in cancer
Frezza, C., Pollard, P. J., & Gottlieb, E. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0728-4 · Cited by 147
“Also, more recently, mutations in SDHA and the SDH assembly factor SDHAF2 (formerly known as SDH5 and required for flavination of SDH) have been described in hPGL [9–11].”
BackgroundChinopoulos, C. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23196 · Cited by 148
“…pathway in which cancer finds metabolic support when growing in hypoxic environments, while also exhibiting a number of defects in the electron transport chain (Tomlinson et al., 2002; Hao et al., 2009; Linehan et al., 2010; Weinberg et al., 2010), rendering its harboring mitochondria defective.”
BackgroundMorandi, A., Taddei, M. L., Chiarugi, P., & Giannoni, E. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00040 · Cited by 146
Turková, H., Prodanov, T., Malý, M., Martucci, V. L., Adams, K. T., Widimsky, J., Jr., Chen, C. C., Ling, A. L., Kebebew, E., Stratakis, C. A., et al. (2015) · Endocrine Practice · doi:10.4158/ep15725.or · Cited by 143
“Germline mutations in SDHAF2 (encoding SDH complex assembly factor 2) have been linked to an inherited tumor syndrome (7).”
BackgroundThe role of complex II in disease
Hoekstra, A. S., & Bayley, J. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.11.005 · Cited by 145
Self-citationGenetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma
Muth, A., Crona, J., Gimm, O., Elmgren, A., Filipsson, K., Stenmark‐Askmalm, M., Sandstedt, J., Tengvar, M., & Tham, E. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12869 · Cited by 135
Parenti, G., Zampetti, B., Rapizzi, E., Ercolino, T., Giaché, V., & Mannelli, M. (2012) · Journal of Oncology · doi:10.1155/2012/872713 · Cited by 126
“This group of genes includes those encoding the four subunits (A, B, C, and D) of the succinate dehydrogenase (SDH) [55–58], the recently identified gene SDHAF2, which is responsible for the flavination of the SDHA subunit [59], and the very recently discovered TMEM127 [60] and MAX [61], both mainly related to bilater…”
BackgroundIsocitrate Dehydrogenase Mutations Are Rare in Pheochromocytomas and Paragangliomas
Gaal, J., Burnichon, N., Korpershoek, E., Roncelin, I., Bertherat, J. Y., Plouin, P., de Krijger, R. R., Gimenez‐Roqueplo, A., & Dinjens, W. N. M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2170 · Cited by 131
Metadata
- Authors
- Hao, H.-X., Khalimonchuk, O., Schraders, M., Dephoure, N., Bayley, J.-P., Kunst, H., Devilee, P., Cremers, C. W. R. J., Schiffman, J. D., Bentz, B. G., Gygi, S. P., Winge, D. R., Kremer, H., & Rutter, J.
- Affiliations
- University of Utah (US)
- Radboud University Medical Center (NL)
- Harvard University (US)
- Leiden University Medical Center (NL)
- Corresponding author
- Rutter, Jared
- ORCID
- Venue
- Science
- Published
- 2009-08-28
- Volume
- 325
- Issue
- 5944
- Pages
- 1139-1142
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3881419
- OpenAlex
- W2028117213
- Cited by
- 702
- References
- 26
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 12 · 2023: 26 · 2022: 31 · 2021: 29 · 2020: 37 · 2019: 39 · 2018: 38 · 2017: 47 · 2016: 42 · 2015: 48 · 2014: 64 · 2013: 68 · 2012: 76
- FWCI
- 65.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM087346, GM087346)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK071962)
- National Institute of Environmental Health Sciences (R01ES003817)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- succinate dehydrogenase, flavin adenine dinucleotide, paraganglioma, hereditary paraganglioma, germline mutations, mitochondrial proteins, cancer susceptibility genes, mitochondrial electron transport chain, TCA cycle, yeast model
- MeSH terms
- Amino Acid Sequence, Cell Line, Flavin-Adenine Dinucleotide, Female, Flavoproteins, Haplotypes, Humans, Male, Mitochondria, Molecular Sequence Data, Oxygen Consumption, Paraganglioma, Pedigree, Saccharomyces cerevisiae, Succinate Dehydrogenase, Germ-Line Mutation, Protein Subunits, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Inheritance Patterns, Proteomics, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
