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Literature summary extracted from
- Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function (2020), Biol. Chem., 401, 319-330 .
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.3.5.1 | additional information | direct effectors are either deactivators such as oxaloacetate or activators such as substrates, anions, reduced quinone, ATP, and reduction | Homo sapiens | |
| 1.3.5.1 | oxaloacetate | the interaction between SDH and oxaloacetate renders the enzyme inactive, while the interaction between the activator and enzyme prevent such interaction with oxaloacetate | Homo sapiens |  |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.3.5.1 | mitochondrion | - |
Mus musculus | 5739 | - |
| 1.3.5.1 | mitochondrion | - |
Rattus norvegicus | 5739 | - |
| 1.3.5.1 | mitochondrion | - |
Homo sapiens | 5739 | - |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.3.5.1 | Fe2+ | within Fe-S clusters | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.3.5.1 | succinate + a quinone | Staphylococcus aureus | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Mus musculus | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Thermus thermophilus | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Rattus norvegicus | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Neisseria meningitidis | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Caenorhabditis elegans | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Mycobacterium tuberculosis | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Brassica sp. | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Escherichia coli | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Homo sapiens | - |
fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | Saccharomyces cerevisiae | - |
fumarate + a quinol | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.3.5.1 | Brassica sp. | - |
- |
- |
| 1.3.5.1 | Caenorhabditis elegans | - |
- |
- |
| 1.3.5.1 | Escherichia coli | P0AC41 AND P07014 | proteins sdhA and sdhB | - |
| 1.3.5.1 | Homo sapiens | P31040 AND P21912 AND Q99643 AND O14521 | proteins SDHA, SDHB, SDHC, and SDHD | - |
| 1.3.5.1 | Mus musculus | - |
- |
- |
| 1.3.5.1 | Mycobacterium tuberculosis | - |
- |
- |
| 1.3.5.1 | Neisseria meningitidis | - |
- |
- |
| 1.3.5.1 | Rattus norvegicus | - |
- |
- |
| 1.3.5.1 | Saccharomyces cerevisiae | Q00711 AND P21801 AND P33421 AND P37298 | proteins SDH1, SDH2, SDH3, and SDH4 | - |
| 1.3.5.1 | Staphylococcus aureus | - |
- |
- |
| 1.3.5.1 | Thermus thermophilus | - |
- |
- |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 1.3.5.1 | acetylation | deacetylation modification of SDHA by SIRT3 (which is reversible by acetylation) increases the activity of SDH complex in mice and human chronic myelogenous leukemia cell lines (K562). SIRT3 is a member of the sirtuin family of NADP-dependent deacetylases in mitochondria which catalyses the deacetylation of various metabolic enzymes and components of oxidative phosphorylation including SDHA subunit. In line with this, acetylating compounds, in vitro, reduced the activity of SDH. Acetylation of the hydrophilic surface of SDHA may govern entrance of the substrate into the active site of the enzyme | Mus musculus |
| 1.3.5.1 | acetylation | deacetylation modification of SDHA by SIRT3 (which is reversible by acetylation) increases the activity of SDH complex in mice and human chronic myelogenous leukemia cell lines (K562). SIRT3 is a member of the sirtuin family of NADP-dependent deacetylases in mitochondria which catalyses the deacetylation of various metabolic enzymes and components of oxidative phosphorylation including SDHA subunit. In line with this, acetylating compounds, in vitro, reduced the activity of SDH. Acetylation of the hydrophilic surface of SDHA may govern entrance of the substrate into the active site of the enzyme. Deacetylation also occurs in histones by histone deacetylases (HDACs). The inhibition of class I HDACs results in higher expression of SDH and promotion of oxidative phosphorylation in skeletal muscles and adipose tissues. Accordingly, class I HDACs cause mitochondrial dysfunction by deregulation of complex I and II (SDH) in cardiomyocyte. Chidamide, a histone deacetylase inhibitor increases SDHA expression, which might have a therapeutic value, as a tumor suppressor, in multiple myeloma patients | Homo sapiens |
| 1.3.5.1 | acetylation | the minor overlap observed between lysine propionylation and acetylation sites in 67 proteins that were both acetylated and propionylated suggests that the two acylation reactions are most likely regulated independently by distinct enzymes and are possibly involved in different functions | Thermus thermophilus |
| 1.3.5.1 | acylation | the posttranslational modification is reported to occur in SDHA subunit of Thermus thermophilus. The minor overlap observed between lysine propionylation and acetylation sites in 67 proteins that are both acetylated and propionylated suggests that the two acylation reactions are most likely regulated independently by distinct enzymes and are possibly involved in different functions | Thermus thermophilus |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Staphylococcus aureus |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Mus musculus |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Thermus thermophilus |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Rattus norvegicus |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Neisseria meningitidis |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Caenorhabditis elegans |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Mycobacterium tuberculosis |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Brassica sp. |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Escherichia coli |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Homo sapiens |
| 1.3.5.1 | additional information | posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation | Saccharomyces cerevisiae |
| 1.3.5.1 | phosphoprotein | FGR tyrosine kinase is one of the kinases that target SDHA at positions Y535 and Y596 (of rat sequence). ROS mediates the activation of FGR tyrosine kinase which phosphorylates SDHA at Y604 and that this function of FGR is required for the adjustment of metabolism under various conditions such as nutrient restriction, hypoxia/reoxygenation, and T-cell activation. This regulation together with the function of phagosomal NADPH oxidase (a source of ROS generation) seems to be essential for the activation of anti-bacterial response in macrophages through committing complex I and II (SDH) to respiration rather than their assembly. Additional to FGR, c-Src is another mitochondrial tyrosine kinase which targets both NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr193 of respiratory complex I and SDHA at Tyr215 of complex II. NDUFV2 phosphorylation is required for NADH dehydrogenase activity, which affects both respiration and cellular ATP content. SDHA phosphorylation, on the other hand, does not alter the enzyme activity but disconcerts electron transfer resulting in the generation of reactive oxygen species. The T98G cell line and the primary neurons expressing the mutants at the corresponding Tyr residues loose viability. These observations thus propound that the mitochondrial c-Src modulates oxidative phosphorylation by phosphorylating two respiratory components and that c-Src activity is essential for cell viability. Dephosphorylation of SDHA is exemplified by PTEN-like mitochondrial phosphatase-1 (PTPMT1), an enzyme which dephosphorylates phosphatidylglycerol phosphate (in cardiolipin biogenesis pathway) and SDHA. Inhibition of PTPMT1 leads to enhanced phosphorylation and activation of SDH and consequently lower glucose concentration. Increased SDH activity lowers glucose levels by at least two mechanisms, by inducing glucose uptake and by boosting the rate of glucose utilization. Collectively these results suggest that PTPMT1 is a major coordinator of glucose utilization by mitochondria | Rattus norvegicus |
| 1.3.5.1 | phosphoprotein | ROS mediates the activation of FGR tyrosine kinase which phosphorylates SDHA at Y604 and that this function of FGR is required for the adjustment of metabolism under various conditions such as nutrient restriction, hypoxia/reoxygenation, and T-cell activation. This regulation together with the function of phagosomal NADPH oxidase (a source of ROS generation) seems to be essential for the activation of anti-bacterial response in macrophages through committing complex I and II (SDH) to respiration rather than their assembly. Additional to FGR, c-Src is another mitochondrial tyrosine kinase which targets both NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr193 of respiratory complex I and SDHA at Tyr215 of complex II. NDUFV2 phosphorylation is required for NADH dehydrogenase activity, which affects both respiration and cellular ATP content. SDHA phosphorylation, on the other hand, does not alter the enzyme activity but disconcerts electron transfer resulting in the generation of reactive oxygen species. The T98G cell line and the primary neurons expressing the mutants at the corresponding Tyr residues loose viability. These observations thus propound that the mitochondrial c-Src modulates oxidative phosphorylation by phosphorylating two respiratory components and that c-Src activity is essential for cell viability. Dephosphorylation of SDHA is exemplified by PTEN-like mitochondrial phosphatase-1 (PTPMT1), an enzyme which dephosphorylates phosphatidylglycerol phosphate (in cardiolipin biogenesis pathway) and SDHA. Inhibition of PTPMT1 leads to enhanced phosphorylation and activation of SDH and consequently lower glucose concentration. Increased SDH activity lowers glucose levels by at least two mechanisms, by inducing glucose uptake and by boosting the rate of glucose utilization. Collectively these results suggest that PTPMT1 is a major coordinator of glucose utilization by mitochondria | Homo sapiens |
| 1.3.5.1 | succinylation | the posttranslational modification converts the cationic lysine side chain to an anion with diverse implications for protein structure and function. Systematic profiling of the mammalian succinylome, identifies SDHA and SDHB as two succinylated proteins. Most of the succinylation sites identified across the succinylome have no overlap with acetylation sites, suggesting differential regulation of succinylation and acetylation | Homo sapiens |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.3.5.1 | cardiac muscle fiber | - |
Homo sapiens | - |
| 1.3.5.1 | myoblast | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.3.5.1 | succinate + a quinone | - |
Staphylococcus aureus | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Mus musculus | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Thermus thermophilus | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Rattus norvegicus | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Neisseria meningitidis | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Caenorhabditis elegans | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Mycobacterium tuberculosis | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Brassica sp. | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Escherichia coli | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Homo sapiens | fumarate + a quinol | - |
? | |
| 1.3.5.1 | succinate + a quinone | - |
Saccharomyces cerevisiae | fumarate + a quinol | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.3.5.1 | complex II | - |
Staphylococcus aureus |
| 1.3.5.1 | complex II | - |
Mus musculus |
| 1.3.5.1 | complex II | - |
Thermus thermophilus |
| 1.3.5.1 | complex II | - |
Rattus norvegicus |
| 1.3.5.1 | complex II | - |
Neisseria meningitidis |
| 1.3.5.1 | complex II | - |
Caenorhabditis elegans |
| 1.3.5.1 | complex II | - |
Mycobacterium tuberculosis |
| 1.3.5.1 | complex II | - |
Brassica sp. |
| 1.3.5.1 | complex II | - |
Escherichia coli |
| 1.3.5.1 | complex II | - |
Homo sapiens |
| 1.3.5.1 | complex II | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SDH | - |
Staphylococcus aureus |
| 1.3.5.1 | SDH | - |
Mus musculus |
| 1.3.5.1 | SDH | - |
Thermus thermophilus |
| 1.3.5.1 | SDH | - |
Rattus norvegicus |
| 1.3.5.1 | SDH | - |
Neisseria meningitidis |
| 1.3.5.1 | SDH | - |
Caenorhabditis elegans |
| 1.3.5.1 | SDH | - |
Mycobacterium tuberculosis |
| 1.3.5.1 | SDH | - |
Brassica sp. |
| 1.3.5.1 | SDH | - |
Escherichia coli |
| 1.3.5.1 | SDH | - |
Homo sapiens |
| 1.3.5.1 | SDH | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SDH1 | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SDH2 | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SDH3 | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SDH4 | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | SdhA | - |
Mus musculus |
| 1.3.5.1 | SdhA | - |
Rattus norvegicus |
| 1.3.5.1 | SdhA | - |
Escherichia coli |
| 1.3.5.1 | SdhA | - |
Homo sapiens |
| 1.3.5.1 | SDHB | - |
Mus musculus |
| 1.3.5.1 | SDHB | - |
Rattus norvegicus |
| 1.3.5.1 | SDHB | - |
Escherichia coli |
| 1.3.5.1 | SDHB | - |
Homo sapiens |
| 1.3.5.1 | SdhC | - |
Mus musculus |
| 1.3.5.1 | SdhC | - |
Rattus norvegicus |
| 1.3.5.1 | SdhC | - |
Homo sapiens |
| 1.3.5.1 | SdhD | - |
Mus musculus |
| 1.3.5.1 | SdhD | - |
Rattus norvegicus |
| 1.3.5.1 | SdhD | - |
Homo sapiens |
| 1.3.5.1 | SQR | - |
Staphylococcus aureus |
| 1.3.5.1 | SQR | - |
Mus musculus |
| 1.3.5.1 | SQR | - |
Thermus thermophilus |
| 1.3.5.1 | SQR | - |
Rattus norvegicus |
| 1.3.5.1 | SQR | - |
Neisseria meningitidis |
| 1.3.5.1 | SQR | - |
Caenorhabditis elegans |
| 1.3.5.1 | SQR | - |
Mycobacterium tuberculosis |
| 1.3.5.1 | SQR | - |
Brassica sp. |
| 1.3.5.1 | SQR | - |
Escherichia coli |
| 1.3.5.1 | SQR | - |
Homo sapiens |
| 1.3.5.1 | SQR | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | succinate dehydrogenase | - |
Staphylococcus aureus |
| 1.3.5.1 | succinate dehydrogenase | - |
Mus musculus |
| 1.3.5.1 | succinate dehydrogenase | - |
Thermus thermophilus |
| 1.3.5.1 | succinate dehydrogenase | - |
Rattus norvegicus |
| 1.3.5.1 | succinate dehydrogenase | - |
Neisseria meningitidis |
| 1.3.5.1 | succinate dehydrogenase | - |
Caenorhabditis elegans |
| 1.3.5.1 | succinate dehydrogenase | - |
Mycobacterium tuberculosis |
| 1.3.5.1 | succinate dehydrogenase | - |
Brassica sp. |
| 1.3.5.1 | succinate dehydrogenase | - |
Escherichia coli |
| 1.3.5.1 | succinate dehydrogenase | - |
Homo sapiens |
| 1.3.5.1 | succinate dehydrogenase | - |
Saccharomyces cerevisiae |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Staphylococcus aureus |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Mus musculus |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Thermus thermophilus |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Rattus norvegicus |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Neisseria meningitidis |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Caenorhabditis elegans |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Mycobacterium tuberculosis |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Brassica sp. |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Escherichia coli |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Homo sapiens |
| 1.3.5.1 | succinate:quinone oxidoreductase | - |
Saccharomyces cerevisiae |
Expression
| EC Number | Organism | Comment | Expression |
|---|---|---|---|
| 1.3.5.1 | Escherichia coli | fnr and arcA gene products both act to repress SDHC expression in response to oxygen. The EIICBGlc protein (the ptsG gene product) is a crucial mediator of the repression of the sdhCDAB operon in the presence of glucose. It acts via the transcription factor crp, which directly regulates expression of the sdhCDAB operon. The glucose repression of this operon occurs in a cAMP-dependent manner | down |
| 1.3.5.1 | Neisseria meningitidis | in Neisseria meningitides low iron condition leads to high expression of NrrF. The latter is an sRNA that targets sdhCDAB transcript and promotes its degradation with the assistance of Hfq chaperone. The concentration of iron is sensed by Fur which represses the genes responsible for iron uptake with the assistance of ferrous iron as a corepressor | down |
| 1.3.5.1 | Homo sapiens | low levels of NFR-1 downregulate SDHA and thereby SDH complex expression. This stabilizes HIF-1 and promotes its nuclear translocation and high expression of glucose transporters and heme oxygenase-1. Deacetylation also occurs in histones by histone deacetylases (HDACs). The inhibition of class I HDACs results in higher expression of SDH and promotion of oxidative phosphorylation in skeletal muscles and adipose tissues. Chidamide, a histone deacetylase inhibitor increases SDHA expression | down |
| 1.3.5.1 | Brassica sp. | in Brassica hexaploids transcriptions of SDH genes are activated by long non-coding RNAs possibly to stimulate energy production via TCA cycle | up |
| 1.3.5.1 | Saccharomyces cerevisiae | in yeast, glucose represses the transcription of SDH2 (SDHB homologue) by a mechanism in which the upstream promoter sequence of SDHB, containing four regulatory elements, is shown to interact with the HAP2/3/4 transcription activator complex. Maximum expression of SDH1 (SDHA homologue) and SDH3 (SDHC homologue) require the same transcription activator. Accordingly, the expression of SDH1 and SDH3 is enhanced 5 times more strongly on galactose than on glucose. Likewise, an increase in the abundance of SDH4 (SDHD homologue) mRNA observed in media containing galactose rather than glucose. Therefore it seems that the same transcription activator complex regulates the transcription of all 4 genes encoding subunits of SDH | up |
| 1.3.5.1 | Homo sapiens | the nuclear respiratory factor-1 (NRF-1) induces SDH expression through binding to the gene promoters of SDHA and SDHD in the aerobic cardiomyocyte | up |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species | Brassica sp. |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Staphylococcus aureus |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Mus musculus |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Thermus thermophilus |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Rattus norvegicus |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Neisseria meningitidis |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Caenorhabditis elegans |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Mycobacterium tuberculosis |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Escherichia coli |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Homo sapiens |
| 1.3.5.1 | evolution | the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells | Saccharomyces cerevisiae |
| 1.3.5.1 | malfunction | impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. Defective SDH leads to tumorigenesis, where accumulated succinate promotes HIF-1 stabilization. In humans, another regulatory mechanism through alternative splicing of SDHC transcript is reported in which a shorter isoform of SDHC (DELTA5 lacking exon 5) is produced which lacks heme binding region and therefore has no function. This results in significant downregulation of SDH complex. This variant of SDHC may, therefore, act as a dominant-negative inhibitor of full-length SDHC. DELAT5 may have a role in the pathogenesis of tumorigenesis associated with the malfunction of SDH. A posttranscriptional regulation has been described in late stages of lung cancer in which miR-210 (a microRNA) is overexpressed in normoxia. miR-210 targets SDHD and other transcripts of complex I and II such as NDUAF4 eventually leading to mitochondrial dysfunction and cell death. miR-210-dependent targeting of SDHD transcript activates HIF-1 and in agreement with earlier findings links loss-of-function SDH mutations to HIF-1 stabilization. A mutation in K547 of SDHA (which is typically desuccinylated by SIRT5) renders SDHA unable to interact with SDH5 and thereby made SDH inactive. Furthermore, SIRT5 promotes clear cell renal cell carcinoma (ccRCC) proliferation through inactivation of SDH and switching metabolism to aerobic glycolysis | Homo sapiens |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Staphylococcus aureus |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Mus musculus |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Thermus thermophilus |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Rattus norvegicus |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Neisseria meningitidis |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Caenorhabditis elegans |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Mycobacterium tuberculosis |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Brassica sp. |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Escherichia coli |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Homo sapiens |
| 1.3.5.1 | metabolism | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP | Saccharomyces cerevisiae |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen. In Escherichia coli a EIICBGlc protein (the ptsG gene product) is identified, that is a component of the major glucose transport machinery known as phosphoenolpyruvate (PEP) phosphotransferase system (PTS), and a crucial mediator of the repression of the sdhCDAB operon in the presence of glucose. It acts via the transcription factor crp, which directly regulates expression of the sdhCDAB operon. The glucose repression of this operon occurs in a cAMP-dependent manner | Escherichia coli |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen | Staphylococcus aureus |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen | Mycobacterium tuberculosis |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen. In Neisseria meningitides low iron condition leads to high expression of NrrF. The latter is an sRNA that targets sdhCDAB transcript and promotes its degradation with the assistance of Hfq chaperone. The concentration of iron is sensed by Fur which represses the genes responsible for iron uptake with the assistance of ferrous iron as a corepressor | Neisseria meningitidis |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case, fnr and arcA gene products both act to repress SDHC expression in response to oxygen | Thermus thermophilus |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In yeast, glucose represses the transcription of SDH2 (SDHB homologue) by a mechanism in which the upstream promoter sequence of SDHB containing four regulatory elements is shown to interact with the HAP2/3/4 transcription activator complex. Maximum expression of SDH1 (SDHA homologue) and SDH3 (SDHC homologue) require the same transcription activator. Accordingly, the expression of SDH1 and SDH3 is enhanced 5 times more strongly on galactose than on glucose. Likewise, an increase in the abundance of SDH4 (SDHD homologue) mRNA observed in media containing galactose rather than glucose. Therefore it seems that the same transcription activator complex regulates the transcription of all 4 genes encoding subunits of SDH. The 5'-untranslated region (5' UTR) of the SDH2 mRNA contains a major determinant which controls its differential turnover in media containing glycerol versus glucose. Furthermore, the 5' exonuclease encoded by the XRN1 gene is necessary for the rapid degradation of the SDH1 and SDH2 mRNAs in the presence of glucose | Saccharomyces cerevisiae |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In Brassica hexaploids transcriptions of SDH genes are activated by long non-coding RNAs possibly to stimulate energy production via TCA cycle | Brassica sp. |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In human cells, the nuclear respiratory factor-1 (NRF-1) initially is the primary transcriptional regulator of mitochondrial biogenesis. NRF-1 also induces SDH expression through binding to the gene promoters of SDHA and SDHD in the aerobic cardiomyocyte. Low levels of NFR-1 downregulate SDHA and thereby SDH complex expression. This stabilizes HIF-1 and promotes its nuclear translocation and high expression of glucose transporters and heme oxygenase-1. Transcription of the genes encoding SDH subunits (particularly SDHB) of human myoblast cells requires NRF-1 and NRF-2 transcription factors. Certain levels of desuccinylase SIRT5 are required for physiological activity of SDH and any imbalance i.e. either too low or too high levels, may influence SDH activity. Direct effectors are either deactivators such as oxaloacetate or activators such as substrates, anions, reduced quinone, ATP, and reduction. The interaction between SDH and oxaloacetate renders the enzyme inactive, while the interaction between the activator and enzyme prevent such interaction with oxaloacetate | Homo sapiens |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview | Mus musculus |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview | Rattus norvegicus |
| 1.3.5.1 | physiological function | succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview | Caenorhabditis elegans |
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