Affinage

SDHA

Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial · UniProt P31040

Length
664 aa
Mass
72.7 kDa
Annotated
2026-06-10
98 papers in source corpus 24 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SDHA encodes the catalytic flavoprotein subunit of mitochondrial complex II (succinate dehydrogenase), whose enzymatic activity oxidizes succinate to fumarate and links the TCA cycle to the electron transport chain (PMID:16195397, PMID:22972948). Maturation of SDHA requires covalent flavination: structural and biochemical reconstitution show that the dedicated assembly factor SDHAF2, acting in synergy with a small-molecule dicarboxylate cofactor, reorients the flavin and capping domains and adjusts the pKa of R451 to support covalent FAD attachment (PMID:32887801), and flavinated SDHA is in turn required for productive complexation with and stabilization of SDHB (PMID:37945749, PMID:21505157, PMID:22974104, PMID:23612575). SDHA loss-of-function abolishes complex II assembly and activity, causing succinate accumulation that inhibits HIF prolyl hydroxylases and drives normoxic (pseudo-hypoxic) HIF-1alpha stabilization in a manner controlled by the succinate/alpha-ketoglutarate ratio and independent of ROS and iron availability (PMID:16195397, PMID:20484225); this establishes SDHA as a tumor suppressor whose biallelic or splicing/missense mutations cause isolated complex II deficiency and disease (PMID:20484225, PMID:24781757, PMID:22972948). Notably, proximal inhibition at SDHA differs mechanistically from distal SDHB/C/D loss, failing to elevate ROS and instead reducing cell growth (PMID:17967865), and accumulated metabolites can act through additional effectors including YAP/TAZ stabilization via cullin1 deNEDDylation (PMID:35713976) and fumarate-driven KEAP1-Nrf2 inflammatory signaling (PMID:31527833). SDHA expression and activity are tightly regulated: NRF-1 transcriptionally controls SDHA promoter activity (PMID:18252725), and the protein is post-translationally tuned by SIRT5-mediated desuccinylation at K547 (inhibitory, via disruption of SDHAF2 binding) (PMID:30703481), SIRT3-mediated deacetylation (activating) (PMID:38087172), HINT3/HDAC1-controlled acetylation at K335 (PMID:40755357), and CAV1-mediated ubiquitin-proteasomal degradation (PMID:37804808). Reciprocally, SDHA binding protects its assembly factor SDHAF2 from LON protease degradation (PMID:24414418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Established the central mechanism by which SDHA loss causes disease: that SDH deficiency raises succinate and stabilizes HIF-1alpha under normoxia, distinguishing this from ROS- or iron-dependent routes.

    Evidence Cell-based assays in SDHA-mutant fibroblasts with HIF-1alpha localization and alpha-KG rescue

    PMID:16195397

    Open questions at the time
    • Did not resolve which prolyl hydroxylase isoform is rate-limiting
    • Did not establish in vivo tumorigenic consequences
  2. 2007 High

    Distinguished the mechanism of SDHA (proximal) loss from SDHB/C/D (distal) loss, showing SDHA knockdown does not elevate ROS or HIF-alpha and instead reduces growth.

    Evidence Reciprocal RNAi of complex II subunits with ROS, HIF, and growth readouts in vitro and in vivo

    PMID:17967865

    Open questions at the time
    • Apparent contradiction with later HIF-1alpha stabilization findings in SDHA-mutant cells not fully reconciled
    • Molecular basis of differential ROS production between subunits unresolved
  3. 2008 High

    Identified transcriptional control of SDHA, showing NRF-1 binds the SDHa promoter and regulates complex II expression with downstream HIF-1alpha consequences.

    Evidence Promoter analysis, ChIP, NRF-1/SDHa silencing, and HIF-1alpha localization in cardiomyocytes

    PMID:18252725

    Open questions at the time
    • Co-regulators at the SDHa promoter not defined
    • Tissue specificity of NRF-1 control not established
  4. 2010 High

    Formally established SDHA as a tumor suppressor by tying a germline mutation to loss of enzymatic activity, pseudo-hypoxia, and angiogenesis.

    Evidence IHC, yeast complementation, enzyme assay, transcriptomics and LOH on a p.Arg589Trp tumor

    PMID:20484225

    Open questions at the time
    • Single mutation studied
    • Tissue-specific penetrance of SDHA tumorigenesis not addressed
  5. 2012 Medium

    Showed that SDHA protein is required for SDHB stability and complex II assembly, providing a structural rationale for combined subunit loss in patients.

    Evidence Western blot, IHC, BN-PAGE, and yeast complementation in GIST and complex II-deficient patient samples

    PMID:21505157 PMID:22972948 PMID:22974104 PMID:23612575

    Open questions at the time
    • Did not define the stoichiometric/structural basis of SDHB destabilization
    • Whether residual SDHA fragments retain partial function unclear
  6. 2014 High

    Revealed a reciprocal stabilization mechanism: SDHA binding protects assembly factor SDHAF2 from LON protease degradation, and a paraganglioma mutation breaks this interaction.

    Evidence Import-chase in isolated mitochondria, in vitro LON degradation assay, BN-PAGE, and LONM depletion

    PMID:24414418

    Open questions at the time
    • Quantitative contribution of this stabilization to flavination kinetics not measured
    • Other proteases not excluded
  7. 2019 Medium

    Defined post-translational regulation of SDHA activity, showing SIRT5 desuccinylates K547 to suppress activity by impairing SDHAF2 binding.

    Evidence Succinylome MS, K547R mutagenesis, Co-IP, enzyme activity assays, and SIRT5 knockdown in ccRCC cells

    PMID:30703481

    Open questions at the time
    • Single lab
    • Stoichiometry of endogenous K547 succinylation in normal tissue not quantified
  8. 2019 Medium

    Expanded SDHA pathology beyond loss-of-function by linking gain-of-function variants to fumarate accumulation and KEAP1-Nrf2 inflammatory signaling.

    Evidence Exome sequencing, respirometry, fumarate metabolite profiling, Nrf2 target analysis, and in vivo IL-6 blockade in PPBL patients

    PMID:31527833

    Open questions at the time
    • Molecular basis of how variants produce gain-of-function unclear
    • Single patient cohort
  9. 2020 High

    Solved how SDHA acquires its FAD cofactor: a structure showing SDHAF2 plus a dicarboxylate cofactor reorient the flavin/capping domains and tune R451 pKa for covalent flavination.

    Evidence X-ray crystallography of the SDHA-SDHAF2 complex with biochemical reconstitution and mutagenesis

    PMID:32887801

    Open questions at the time
    • Order of flavination relative to SDHB incorporation in vivo not fully resolved
    • Identity/source of the physiological dicarboxylate not established
  10. 2022 Medium

    Identified a HIF-independent oncogenic route, in which SDHA/B loss-derived succinate deNEDDylates cullin1 to stabilize YAP/TAZ.

    Evidence RNA-seq, depletion/succinate exposure, NEDDylation and Co-IP assays, and tumor growth assays in HCC

    PMID:35713976

    Open questions at the time
    • Direct succinate target on the deNEDDylation machinery not identified
    • Single lab
  11. 2023 Medium

    Showed SIRT3 deacetylation activates complex II and is protective, linking SDHA acetylation status to neuronal injury.

    Evidence Rotenone PD rat/MN9D models with SIRT3 modulation, SDHA overexpression, activity and acetylation readouts

    PMID:38087172

    Open questions at the time
    • Specific acetylated lysines not mapped
    • Direct vs indirect SIRT3-SDHA action not distinguished
  12. 2023 Medium

    Demonstrated CAV1 directly binds SDHA and drives its ubiquitin-proteasomal degradation, coupling lipotoxic stress to mitochondrial dysfunction.

    Evidence Reciprocal Co-IP, ubiquitination assay, CAV1/SDHA epistasis knockdowns, and db/db mouse model

    PMID:37804808

    Open questions at the time
    • E3 ligase mediating CAV1-dependent SDHA ubiquitination not identified
    • Single lab
  13. 2023 Medium

    Connected SDHA flavination state to SDHB levels and cellular metabolism, showing low flavinated SDHA reduces SDHB in cancer cells.

    Evidence Autofluorescence spectroscopy, SDHA/SDHB quantification, and metabolic profiling in OSCC cells

    PMID:37945749

    Open questions at the time
    • Cause of reduced flavination in OSCC not defined
    • Single lab
  14. 2024 Medium

    Translated mechanistic knowledge into a functional pathogenicity classifier, scoring SDHA missense variants by enzymatic dysfunction.

    Evidence SDHA-knockout cell line with Bxb1 variant reintroduction and SDH activity-based logistic regression on 72 variants

    PMID:39321216

    Open questions at the time
    • Does not capture non-enzymatic (e.g. gain-of-function or assembly) variant effects
    • Single lab assay
  15. 2025 Medium

    Added an acetylation-control axis, with HINT3 suppressing HDAC1 to maintain SDHA K335 acetylation and restrain SDH activity and ROS in cardiac ischemia-reperfusion.

    Evidence Cardiac I/R mouse model with cardiomyocyte HINT3 KO/OE, Co-IP, K335 acetylation, and SDH activity assays

    PMID:40755357

    Open questions at the time
    • Direct vs indirect HINT3-HDAC1-SDHA wiring not fully dissected
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple, sometimes opposing regulatory inputs on SDHA (acetylation, succinylation, ubiquitination, transcription) are integrated in a given tissue and reconciled with the divergent ROS/HIF outcomes of proximal versus distal complex II loss remains unresolved.
  • No unified model integrating PTM crosstalk on SDHA
  • Tissue-specific dominance of each regulator undetermined
  • Quantitative relationship between flavination, assembly, and downstream succinate signaling not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0016740 transferase activity 2
Localization
GO:0005739 mitochondrion 4
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 5 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CAV1HINT3LONP1NRF1SDHAF2SDHBSIRT3SIRT5
Complex memberships
mitochondrial complex II (succinate dehydrogenase)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 X-ray crystal structure of human SDHA in complex with its dedicated assembly factor SDHAF2 was determined. A small-molecule dicarboxylate acts as an essential cofactor that works in synergy with SDHAF2 to orient the flavin and capping domains of SDHA, reorganizing the active site and adjusting the pKa of SDHA R451 to support covalent attachment of the FAD cofactor. Four distinct conformational forms of the complex II flavoprotein were identified and assigned to roles in assembly and catalysis. X-ray crystallography, biochemical reconstitution, structural studies Proceedings of the National Academy of Sciences of the United States of America High 32887801
2005 In fibroblasts carrying SDHA type I mutations, SDH deficiency leads to succinate accumulation and HIF-1alpha nuclear translocation under normoxic conditions (pseudo-hypoxia). This translocation is independent of superoxide production and cellular iron availability but is inhibited by alpha-ketoglutarate, indicating that the succinate/alpha-KG ratio controls HIF-1alpha prolyl hydroxylase activity in SDH-deficient cells. Cell-based assays in SDHA-mutant fibroblasts, HIF-1alpha nuclear translocation assay, alpha-KG supplementation rescue experiments Human molecular genetics High 16195397
2010 A germline SDHA mutation (p.Arg589Trp) causes loss of SDH enzymatic activity in tumor tissue and in a yeast model, and results in pseudo-hypoxia with increased HIF-1alpha and angiogenesis (CD34 upregulation), establishing SDHA as a tumor suppressor gene whose loss-of-function mimics hypoxia via succinate accumulation. Immunohistochemistry, yeast complementation model, in vitro enzymatic activity assay, microarray transcriptome analysis, LOH analysis Human molecular genetics High 20484225
2007 Proximal inhibition of complex II at SDHA (by RNA interference or pharmacological inhibition) does not increase normoxic ROS production or HIF-alpha stabilization and results in decreased cell growth in vitro and in vivo, in contrast to distal subunit (SdhB) inhibition which increases ROS and HIF-alpha. This distinguishes the mechanism of SDHA loss-of-function from that of SDHB/C/D mutations. RNA interference knockdown, pharmacological complex II inhibition, ROS measurement, HIF-alpha stabilization assay, in vitro and in vivo growth assays Molecular and cellular biology High 17967865
2008 Nuclear respiratory factor-1 (NRF-1) binds the promoters of SDHa and SDHd (but not SDHB or SDHC) and transcriptionally regulates Complex II expression. NRF-1 silencing specifically decreases SDHa expression, inactivates Complex II, and leads to aerobic HIF-1alpha stabilization and nuclear translocation in cardiomyocytes; this is reversible by high alpha-ketoglutarate concentrations and independent of mitochondrial ROS. Promoter analysis, gene silencing (NRF-1 and SDHa), chromatin immunoprecipitation (ChIP), HIF-1alpha localization assay, succinate oxidation assay The Journal of biological chemistry High 18252725
2014 The assembly factor SDH5/SDHAF2 is protected from LON protease (LONM)-mediated degradation in mitochondria through its stable interaction with SDHA. SDH5(G78R), a paraganglioma-causing mutation, fails to form a stable complex with SDHA and is rapidly degraded by LONM, establishing that SDHA binding is required to stabilize SDHAF2 from proteolytic turnover. Import-chase analysis in isolated human mitochondria, in vitro LON degradation assay, Blue Native PAGE, LONM depletion experiments FASEB journal High 24414418
2019 SIRT5 desuccinylates SDHA at lysine K547; this desuccinylation by mimetic mutation (K547R) suppresses SDHA enzymatic activity through inhibition of SDH5/SDHAF2 binding, promoting ccRCC cell proliferation. SIRT5 silencing leads to hypersuccinylation and reactivation of SDHA, confirming SIRT5 as the desuccinylase for SDHA at K547. Tandem mass tag labeling/LC-MS/MS succinylome profiling, site-directed mutagenesis (K547R), Co-IP, SDHA enzymatic activity assay, cell proliferation assay, SIRT5 knockdown Free radical biology & medicine Medium 30703481
2023 SIRT3-mediated deacetylation of SDHA activates mitochondrial complex II activity and ATP production; in rotenone-induced PD models, SIRT3 activity is suppressed, leading to SDHA hyperacetylation and impaired complex II activity. Activation of SIRT3 (by icariin or honokiol) or overexpression of SDHA rescues complex II activity and protects neurons from rotenone-induced damage. In vivo rat PD model, in vitro MN9D cell model, SIRT3 activation/inhibition, SDHA overexpression, complex II activity assay, ATP measurement, Western blot for acetylated SDHA Molecular neurobiology Medium 38087172
2022 SDHA/B reduction in HCC leads to succinate accumulation, which facilitates deNEDDylation of cullin1, disrupting the SCF β-TrCP E3 ubiquitin ligase complex, and consequently stabilizing and activating YAP/TAZ. Accelerated cell proliferation and tumor growth caused by SDHA/B depletion or succinate exposure are largely dependent on aberrant YAP/TAZ activation. RNA sequencing, SDHA/B depletion, succinate exposure, Western blot for YAP/TAZ and cullin1 NEDDylation, co-immunoprecipitation, in vitro proliferation and in vivo tumor growth assays Hepatology Medium 35713976
2019 SDHA gain-of-function germline mutations in patients with persistent polyclonal B cell lymphocytosis (PPBL) lead to accumulation of fumarate in B cells, which engages the KEAP1-Nrf2 system to drive transcription of inflammatory cytokine genes, constituting pathological mitochondrial retrograde signaling. Exome sequencing, extracellular acidification/oxygen consumption rate measurement, metabolite profiling (fumarate), Nrf2 target gene expression analysis, in vivo IL-6 blockade trial Nature immunology Medium 31527833
2016 MicroRNA-31 (miR-31) suppresses SDHA expression, vital for mitochondrial electron transport chain complex II; miR-31 overexpression lowers SDHA expression and oxygen consumption rates in partially reprogrammed iPSCs, and co-transduction with Yamanaka factors results in a 2.7-fold increase in full reprogramming, establishing a miR-31/SDHA axis that regulates metabolic switching during reprogramming. miR-31 overexpression, SDHA expression measurement, oxygen consumption rate (Seahorse), iPSC reprogramming efficiency assay (TRA1-60 staining) Stem cell reports Medium 27346679
2023 Flavin adenine dinucleotide (FAD) covalently bound to SDHA (flavinated SDHA) is responsible for autofluorescence changes in the FAD spectral region in oral squamous cell carcinoma cells; lower levels of flavinated SDHA in OSCC cells result in decreased SDHB levels (since flavinated SDHA is required for functional complexation with SDHB) and altered cellular metabolism. Autofluorescence spectroscopy, SDHA/SDHB protein quantification, metabolic profiling, cell-based assays Communications biology Medium 37945749
2025 HINT3 interacts with SDHA and suppresses HDAC1 expression, preventing SDHA deacetylation at K335; this reduces SDH activity and mitochondrial ROS production during cardiac ischemia-reperfusion injury. Cardiomyocyte-specific HINT3 knockout exacerbates myocardial injury and mitochondrial dysfunction, while HINT3 overexpression is protective, establishing the HINT3-HDAC1-SDHA axis in mitochondrial regulation. Mouse cardiac I/R model, cardiomyocyte-specific knockout and overexpression, Co-IP (HINT3-SDHA interaction), HDAC1 expression measurement, SDHA acetylation at K335 assay, SDH activity assay, mitochondrial ROS measurement Advanced science Medium 40755357
2023 CAV1 (Caveolin-1) directly binds SDHA and triggers its ubiquitination and proteasomal degradation, leading to mitochondrial dysfunction and apoptosis in cardiomyocytes under palmitate conditions; silencing CAV1 reduces apoptosis and improves mitochondrial function in a manner blocked by SDHA knockdown. Co-IP (CAV1-SDHA interaction), ubiquitination assay, CAV1 silencing/overexpression, SDHA knockdown, cell viability and apoptosis assays, mitochondrial function assays, in vivo db/db mouse model Biomedicine & pharmacotherapy Medium 37804808
2025 EPAS1 (HIF-2α) increases SDHA expression by inhibiting HDAC2 mRNA expression, thereby increasing acetylation at the SDHA histone H3K27 site; this EPAS1-HDAC2-SDHA axis promotes TCA cycle activity and suppresses glycolysis, inhibiting proliferation and invasion of multiple myeloma cells in vitro and in vivo. EPAS1 overexpression/knockdown, HDAC2 modulation, ChIP for H3K27 acetylation at SDHA locus, SDHA expression assay, metabolic flux (TCA vs glycolysis), in vitro and in vivo proliferation assays NPJ precision oncology Low 41290982
2012 SDHA mutations lead to concurrent loss of both SDHA and SDHB protein expression (demonstrated by Western blotting and immunohistochemistry in GIST patients), indicating that SDHA protein is required for stability of SDHB within the complex II holocomplex. Western blotting, immunohistochemistry, next-generation sequencing, LOH analysis Journal of the National Cancer Institute Medium 21505157 22974104 23612575
2024 Using an SDHA-knockout cell line with Bxb1-mediated variant reintroduction, cancer-associated SDHA missense variants can be distinguished from non-cancer variants by the degree of SDH enzymatic dysfunction they cause; SDH activity data predict cancer pathogenicity with performance exceeding computational tools, providing a functional assay for clinical variant classification. SDHA-knockout cell line, Bxb1-mediated recombination for variant introduction, SDH activity assay, logistic regression for pathogenicity prediction Clinical cancer research Medium 39321216
2014 SDHA splicing mutations (c.64-2A>G and c.1065-3C>A) result in loss of SDHA protein expression; the missense mutation c.565T>G severely affects SDHA enzymatic activity. Pathogenicity of c.565T>G was confirmed by lentiviral complementation experiments in patient fibroblasts. mRNA splicing analysis, protein expression (Western blot), enzymatic activity assay, lentiviral complementation in patient fibroblasts European journal of human genetics Medium 24781757
2012 Recessive SDHA mutations cause isolated complex II deficiency; Western blotting and BN-PAGE studies confirmed decreased steady-state levels of SDH subunits and impaired complex II assembly in patient-derived samples with compound heterozygous SDHA mutations. Western blot, BN-PAGE (Blue Native PAGE), biochemical complex II activity measurement, yeast complementation Journal of medical genetics Medium 22972948
2025 Compound heterozygous SDHA variants (p.R512Q and p.R585W) cause significant decreases in SDH activity, SDH subunit levels, and impaired complex II assembly in patient-derived fibroblasts; additionally, complex I activity and CI-containing supercomplex formation were impaired, though basal and maximal respiration rates remained unchanged while spare respiratory capacity was significantly reduced. Patient-derived fibroblast analysis, SDH enzymatic activity assay, BN-PAGE for assembly, complex I activity assay, Seahorse respirometry Mitochondrion Medium 41833598
2025 Yeast Saccharomyces cerevisiae complementation assays demonstrated that biallelic SDHA mutations found in a pediatric patient with seizures and behavioral dysregulation are functionally deleterious to mitochondrial complex II function. Yeast complementation assay, mitochondrial respiratory chain activity measurement, muscle biopsy biochemistry Clinical genetics Low 40045913
2021 A heterozygous de novo SDHA variant (p.Arg662Cys) causes considerably decreased complex II residual activity in patient-derived fibroblasts and lymphocytes. Protein modeling suggests this substitution compromises FAD-binding to SDHA at the C-terminus, impairing FAD binding and decreasing entire complex II activity. Complex II enzymatic activity assay in patient fibroblasts and lymphocytes, protein structural modeling Metabolic brain disease Low 33471299

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 SDHA is a tumor suppressor gene causing paraganglioma. Human molecular genetics 535 20484225
2007 Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Molecular and cellular biology 364 17967865
2011 SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. The Journal of clinical endocrinology and metabolism 228 21752896
2015 SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 177 25720320
2012 The protein SdhA maintains the integrity of the Legionella-containing vacuole. Proceedings of the National Academy of Sciences of the United States of America 158 22308473
2017 Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. JAMA oncology 152 28384794
2013 Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation. The American journal of surgical pathology 141 23282968
2011 SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. Journal of the National Cancer Institute 120 21505157
2005 Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions. Human molecular genetics 120 16195397
2012 Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 100 22955521
2006 Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA). Journal of neurology, neurosurgery, and psychiatry 99 16361598
2012 Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. Journal of medical genetics 96 22972948
2019 SIRT5-mediated SDHA desuccinylation promotes clear cell renal cell carcinoma tumorigenesis. Free radical biology & medicine 94 30703481
2013 Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors. The American journal of surgical pathology 91 23060355
2007 A novel fur- and iron-regulated small RNA, NrrF, is required for indirect fur-mediated regulation of the sdhA and sdhC genes in Neisseria meningitidis. Journal of bacteriology 91 17351036
2013 Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. European journal of human genetics : EJHG 88 23612575
2013 Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. The Journal of clinical endocrinology and metabolism 86 23633203
2014 SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. European journal of human genetics : EJHG 78 24781757
2012 SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 65 23174939
2018 Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study. The Journal of clinical endocrinology and metabolism 63 29177515
2019 Incidence of succinate dehydrogenase and fumarate hydratase-deficient renal cell carcinoma based on immunohistochemical screening with SDHA/SDHB and FH/2SC. Human pathology 60 31299266
2012 Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wild-type SDHB-negative gastrointestinal stromal tumors. Genes, chromosomes & cancer 60 23109135
2015 A Novel SDHA-deficient Renal Cell Carcinoma Revealed by Comprehensive Genomic Profiling. The American journal of surgical pathology 55 25724004
2012 SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors. BMC cancer 53 22974104
2019 Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma. Frontiers in oncology 50 30854332
2019 SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2. Nature immunology 47 31527833
2019 Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma. Investigative ophthalmology & visual science 43 31596927
2017 SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity. Molecular genetics & genomic medicine 43 28546994
2008 Transcriptional Regulation of SDHa flavoprotein by nuclear respiratory factor-1 prevents pseudo-hypoxia in aerobic cardiac cells. The Journal of biological chemistry 43 18252725
2020 The roles of SDHAF2 and dicarboxylate in covalent flavinylation of SDHA, the human complex II flavoprotein. Proceedings of the National Academy of Sciences of the United States of America 38 32887801
2018 Germline SDHA mutations in children and adults with cancer. Cold Spring Harbor molecular case studies 38 30068732
2014 Mitochondrial matrix proteostasis is linked to hereditary paraganglioma: LON-mediated turnover of the human flavinylation factor SDH5 is regulated by its interaction with SDHA. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 24414418
2013 The Dot/Icm effector SdhA is necessary for virulence of Legionella pneumophila in Galleria mellonella and A/J mice. Infection and immunity 38 23649096
2016 MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism. Stem cell reports 37 27346679
2015 A novel germline mutation in SDHA identified in a rare case of gastrointestinal stromal tumor complicated with renal cell carcinoma. International journal of clinical and experimental pathology 36 26722403
2016 SDHA mutation with dominant transmission results in complex II deficiency with ocular, cardiac, and neurologic involvement. American journal of medical genetics. Part A 35 27683074
2007 Sequence variation in human succinate dehydrogenase genes: evidence for long-term balancing selection on SDHA. BMC biology 34 17376234
2012 Sorbitol dehydrogenase of Aspergillus niger, SdhA, is part of the oxido-reductive D-galactose pathway and essential for D-sorbitol catabolism. FEBS letters 32 22245674
2020 Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF. Nature communications 31 32843629
1985 Cloning and expression in Escherichia coli of sdhA, the structural gene for cytochrome b558 of the Bacillus subtilis succinate dehydrogenase complex. Journal of bacteriology 30 2987185
2022 SDHA/B reduction promotes hepatocellular carcinoma by facilitating the deNEDDylation of cullin1 and stabilizing YAP/TAZ. Hepatology (Baltimore, Md.) 29 35713976
2018 Pathogenicity and Penetrance of Germline SDHA Variants in Pheochromocytoma and Paraganglioma (PPGL). Journal of the Endocrine Society 29 29978154
2009 Subchronic exposure to arsenic decreased Sdha expression in the brain of mice. Neurotoxicology 29 19422848
2000 Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. Molecular and biochemical parasitology 29 10779596
2022 Upregulation of Succinate Dehydrogenase (SDHA) Contributes to Enhanced Bioenergetics of Ovarian Cancer Cells and Higher Sensitivity to Anti-Metabolic Agent Shikonin. Cancers 23 36291881
1985 Cloning and deletion analysis of a genomic segment of Bacillus subtilis coding for the sdhA, B, C (succinate dehydrogenase) and gerE (spore germination) loci. Journal of general microbiology 21 3934334
2023 SIRT3-Mediated Deacetylation of SDHA Rescues Mitochondrial Bioenergetics Contributing to Neuroprotection in Rotenone-Induced PD Models. Molecular neurobiology 20 38087172
2021 SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase. Cell reports 20 34731604
2024 SDHA-related phaeochromocytoma and paraganglioma: review and clinical management. Endocrine-related cancer 15 39133175
2023 SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update. Genes 15 36980917
2023 Lentinan alleviates diabetic cardiomyopathy by suppressing CAV1/SDHA-regulated mitochondrial dysfunction. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 37804808
2023 The MADS-box protein SlTAGL1 regulates a ripening-associated SlDQD/SDH2 involved in flavonoid biosynthesis and resistance against Botrytis cinerea in post-harvest tomato fruit. The Plant journal : for cell and molecular biology 13 37326247
2022 SDHA Germline Variants in Adult Patients With SDHA-Mutant Gastrointestinal Stromal Tumor. Frontiers in oncology 12 35059314
2023 Ginsenoside Rg1 Delays Chronological Aging in a Yeast Model via CDC19- and SDH2-Mediated Cellular Metabolism. Antioxidants (Basel, Switzerland) 11 36829855
2020 LPS1, Encoding Iron-Sulfur Subunit SDH2-1 of Succinate Dehydrogenase, Affects Leaf Senescence and Grain Yield in Rice. International journal of molecular sciences 11 33375756
2000 The nuclear-encoded SDH2-RPS14 precursor is proteolytically processed between SDH2 and RPS14 to generate maize mitochondrial RPS14. Biochemical and biophysical research communications 11 10799306
2022 MicroRNA-16-5p exacerbates sepsis by upregulating aerobic glycolysis via SIRT3-SDHA axis. Cell biology international 10 36153644
2018 Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities. Journal of neuropathology and experimental neurology 10 29850869
2019 Methylsulfonylmethane inhibits cortisol-induced stress through p53-mediated SDHA/HPRT1 expression in racehorse skeletal muscle cells: A primary step against exercise stress. Experimental and therapeutic medicine 9 31853292
2022 PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis. International journal of molecular sciences 7 36232604
2021 A novel de novo heterozygous pathogenic variant in the SDHA gene results in childhood onset bilateral optic atrophy and cognitive impairment. Metabolic brain disease 7 33471299
2014 Corynebacterium glutamicum sdhA encoding succinate dehydrogenase subunit A plays a role in cysR-mediated sulfur metabolism. Applied microbiology and biotechnology 7 24866946
2012 Intraabdominal adhesion formation is associated with differential mRNA expression of metabolic genes PDHb and SDHa. Archives of gynecology and obstetrics 7 22569713
2021 Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/β-catenin pathway. Journal of receptor and signal transduction research 6 33602019
2020 Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor. Pathology, research and practice 6 32534711
2025 Unveiling the hidden role of SDHA in breast cancer proliferation: a novel therapeutic avenue. Cancer cell international 5 40119440
2025 The Role of HINT3 in Myocardial Ischemia-Reperfusion Injury in Male Mice: Mechanisms Involving SDHA and its Acetylation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40755357
2025 Succinate Dehydrogenase Subunit A (SDHA) Mediated Microglia Extracellular Traps Formation Participating in Cerebral Ischemic Reperfusion Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40832885
2024 SDHA secondary findings in germline testing: counseling and surveillance considerations. Endocrine oncology (Bristol, England) 4 38770192
2024 A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants. Clinical cancer research : an official journal of the American Association for Cancer Research 4 39321216
2023 Analysis of the stability of the reference genes GAPDH, SDHA and RPL-19 in sheep from a semi-arid region infected by gastrointestinal nematodes. BMC veterinary research 4 37679739
2021 Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2. European journal of human genetics : EJHG 4 33854214
2020 SDHA-mediated Warburg effect in malignantly transformed human bronchial epithelial cells following long-term exposure to radon. Environmental toxicology 4 32198912
2020 SDHB and SDHA Immunohistochemistry in Canine Pheochromocytomas. Animals : an open access journal from MDPI 4 32957698
2020 Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases. Medicine 4 33031286
2019 First-positive surveillance screening in an asymptomatic SDHA germline mutation carrier. Endocrinology, diabetes & metabolism case reports 4 31368675
2025 Exploring the critical role of SDHA in breast cancer proliferation: implications for novel therapeutic strategies. American journal of translational research 3 40821099
2022 Co-occurrence of VHL and SDHA Pathogenic Variants: A Case Report. Frontiers in oncology 3 35875079
2021 Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum. Molecular genetics & genomic medicine 3 33960148
2020 CYC1, SDHA, UQCRC1, UQCRQ, and SDHB might be important biomarkers in kidney transplant rejection. Clinica chimica acta; international journal of clinical chemistry 3 32302684
2025 Management succinate release through SDHA by G protein-coupled receptor 91 signal, TRAP1, and SIRT3 regulation in lung cancer cells by NAR nanoparticles. Journal, genetic engineering & biotechnology 2 40074439
2025 EPAS1 increases SDHA to inhibit proliferation of multiple myeloma cells by restoring TCA Cycle. NPJ precision oncology 2 41290982
2023 Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers. Communications biology 2 37945749
2022 A Novel Germline SDHA Gene Mutation and Co-Occurring Somatic KIT Activating Mutation in a Patient With Pediatric Central Nervous System Germ Cell Tumor: Case Report. Frontiers in oncology 2 35651799
2021 A case of Carney triad complicated by renal cell carcinoma and a germline SDHA pathogenic variant. Endocrinology, diabetes & metabolism case reports 2 33839693
2025 Impact of SDHA Mutations on Yeast Growth and Mitochondrial Function. Case Study Linking Genetic Findings to Clinical Phenotypes. Clinical genetics 1 40045913
2025 Transcriptional Expression of SLC2A3 and SDHA Predicts the Risk of Local Tumor Recurrence in Patients with Head and Neck Squamous Cell Carcinomas Treated Primarily with Radiotherapy or Chemoradiotherapy. International journal of molecular sciences 1 40141095
2025 The Identification of a Key Regulator of Mitochondrial Metabolism, the LRPPRC Protein, as a Novel Therapeutic Target in SDHA-Overexpressing Ovarian Tumors. Cancers 1 40563592
2025 Structure and expression kinetics of Piscirickettsia salmonis sdhA during infection of Atlantic salmon macrophage-like cells. Fish & shellfish immunology 1 41076213
2024 Combined Germline and Mosaic SDHA Mutation Is Associated With a Multicancer Syndrome Including Neuroblastoma, Renal Cancer, and Multifocal GI Tumor. JCO precision oncology 1 38885448
2023 An unusual paraesophageal and diaphragmatic SDHA-deficient gastrointestinal stromal tumor (GIST) metastases case report. Journal of gastrointestinal oncology 1 36915446
2018 [Mechanisms of recombinant adenovirus-mediated SD-HA fusion protein proliferation inhibition and induced apoptosis of K562 cells]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 29779329
2026 SDHA Deficiency in Hepatocellular Carcinoma Promotes Tumor Progression through Succinate-Induced M2 Macrophage Polarization. Oncology research 0 41613800
2026 To screen or not to screen: complexity of SDHA mutation management. Endocrine oncology (Bristol, England) 0 41635891
2026 Impact of compound heterozygous SDHA variants on mitochondrial function in pediatric with neurological disease. Mitochondrion 0 41833598
2025 Identification of a novel transcript of mouse Sdha. BMC research notes 0 40001192
2025 Effect of Ethylmethylhydroxypyridine Succinate on the Expression of PGC-1α, GR, SUCNR1, and SDHA Genes in the Cerebral Cortex of Old Rats during a Course of Dexamethasone Administration. Bulletin of experimental biology and medicine 0 40679525
2023 Flavinated SDHA Underlies the Change in Intrinsic Optical Properties of Oral Cancers. bioRxiv : the preprint server for biology 0 37577521

Missed literature

Know a paper Affinage missed for SDHA? Flag it for the maintainers and the community.

No submissions yet.