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Literature summary for 1.3.5.1 extracted from
- The assembly of succinate dehydrogenase a key enzyme in bioenergetics (2019), Cell. Mol. Life Sci., 76, 4023-4042 .
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| mitochondrial inner membrane | the catalytic domain (SDH1 and 2) is extrinsic on the matrix side, while the anchor subunits (SDH3 and 4) are intrinsic transmembrane proteins, allowing transfer of the electrons from succinate in the mitochondrial matrix to ubiquinone in the inner membrane | Saccharomyces cerevisiae | 5743 | - |
| mitochondrial inner membrane | the catalytic domain (SDHA and B) is extrinsic on the matrix side, while the anchor subunits (SDHC and D) are intrinsic transmembrane proteins, allowing transfer of the electrons from succinate in the mitochondrial matrix to ubiquinone in the inner membrane | Homo sapiens | 5743 | - |
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| succinate + a quinone | Saccharomyces cerevisiae | - |
fumarate + a quinol | - |
? |  |
| succinate + ubiquinone | Homo sapiens | - |
fumarate + ubiquinol | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P31040 AND P21912 AND Q99643 AND O14521 | proteins SDHA, SDHB, SDHC, and SDHD | - |
| Saccharomyces cerevisiae | Q00711 AND P21801 AND P33421 AND P37298 | proteins SDH1, SDH2, SDH3, and SDH4 | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| succinate + a quinone | - |
Saccharomyces cerevisiae | fumarate + a quinol | - |
? | |
| succinate + ubiquinone | - |
Homo sapiens | fumarate + ubiquinol | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | SDH complex structure and assembly, detailed overview. Succinate dehydrogenase in eukaryotes is composed of four subunits SDH1-4 | Saccharomyces cerevisiae |
| More | SDH complex structure and assembly, detailed overview. Succinate dehydrogenase in eukaryotes is composed of four subunits SDHA-D (human). The SDHA subunit is a flavoprotein containing a covalently bound FAD cofactor and the binding site for dicarboxylates (e.g. succinate). SDHB is an iron-sulfur cluster protein containing three Fe-S clusters. SDHA and SDHB make up the catalytic domain. They extend out into the matrix and constitute the hydrophilic head. SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them. SDHB is sandwiched between SDHA on the matrix side, and SDHC and SDHD in the membrane. These two transmembrane subunits thus form the hydrophobic anchor. A small patch of the anchor is exposed on the distal side, to the aqueous intermembrane space. Therefore, the structure of SDH can be divided into two main modules: SDHA and SDHB as the membrane extrinsic (soluble) domain, and SDHC and SDHD as the membrane domain. The interface between the catalytic head domain and the anchor subunits can be separated without the use of detergent, making the catalytic domain an extrinsic membrane protein | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| complex II | - |
Homo sapiens |
| complex II | - |
Saccharomyces cerevisiae |
| SDH | - |
Homo sapiens |
| SDH | - |
Saccharomyces cerevisiae |
| SDH1 | - |
Saccharomyces cerevisiae |
| SDH2 | - |
Saccharomyces cerevisiae |
| SDH3 | - |
Saccharomyces cerevisiae |
| SDH4 | - |
Saccharomyces cerevisiae |
| SdhA | - |
Homo sapiens |
| SDHB | - |
Homo sapiens |
| SdhC | - |
Homo sapiens |
| SdhD | - |
Homo sapiens |
| SQR | - |
Homo sapiens |
| SQR | - |
Saccharomyces cerevisiae |
| succinate dehydrogenase | - |
Homo sapiens |
| succinate dehydrogenase | - |
Saccharomyces cerevisiae |
| succinate:quinone oxidoreductase | - |
Homo sapiens |
| succinate:quinone oxidoreductase | - |
Saccharomyces cerevisiae |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| FAD | covalently bound in the SDHA subunit, for electrons travel from FAD in SDHA, via three Fe-S clusters in SDHB, to the quinone-binding site at the membrane interface. Significance of FAD covalent bond versus non-covalent bond. FAD is mandatory for enzyme activity. In yeast, a soluble, mitochondrial matrix protein named Sdh5 is required for the activation and flavination of Sdh1 (SDH flavoprotein subunit homologue) as well as for SDH-dependent respiration | Saccharomyces cerevisiae | |
| FAD | covalently bound in the SDHA subunit, for electrons travel from FAD in SDHA, via three Fe-S clusters in SDHB, to the quinone-binding site at the membrane interface. Significance of FAD covalent bond versus non-covalent bond. FAD is mandatory for enzyme activity. Under aerobic conditions, the FAD moiety catalyzes succinate oxidation, upon which FAD is itself reduced to FADH2. Changes in redox potential prompt electrons to move from the reduced FADH2 through Fe-S clusters in SdhB to eventually reduce ubiquinone at the ubiquinone-binding site formed by SdhC and SdhD | Homo sapiens | |
| Fe-S cluster | SDHB is an iron-sulfur cluster protein containing three Fe-S clusters | Homo sapiens | |
| Fe-S cluster | SDHB is an iron-sulfur cluster protein containing three Fe-S clusters | Saccharomyces cerevisiae | |
| heme | SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them | Homo sapiens | |
| heme | SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them | Saccharomyces cerevisiae | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | the yeast cells lacking SDH5 gene can grow in fermentative mode (i.e. in glucose), but fail to grow in respiratory mode (e.g. in glycerol) which is an indication of a defective oxidative phosphorylation. This phenotype can be rescued by expression of SDH5. Other phenotypes of sdh5DELTA yeast cells include: substantially decreased levels of all four SDH subunits, impaired oxygen consumption (similar to the respiratory-deficient sdh1DELTA cells), respiration-related phenotypes of H2O2 hypersensitivity and reduced chronological life-span. Another phenotype is acetate hyper-excretion which is shared by four other TCA cycle mutants. A yeast strain lacking SDHAF1 homologue Sdh6 is OXPHOS incompetent. Transformation of this strain with YDR379C-A variants corresponding to the human mutant alleles do not recover OXPHOS growth, indicating that these mutations cause the disease. Yeast lacking SDHAF3 exhibits defective SDH activity and reduced levels of Sdh2 | Saccharomyces cerevisiae |
| metabolism | succinate dehydrogenase (SDH) is one of the most important enzymes involved in the in three cellular processes: glycolysis, the tricarboxylic acid cycle (TCA cycle, Krebs cycle) and oxidative phosphorylation (OXPHOS). SDH, also known as complex II or succinate:ubiquinone oxidoreductase (SQR) is a unique enzyme in four ways: first, it is involved in both the TCA and OXPHOS in mitochondria. Second, all the genes for mitochondrial SDH are nuclear. Third, it is the only membrane-bound component of TCA cycle. Fourth, it is the smallest and the only complex of mitochondrial electron transport chain (ETC) which does not directly extrude protons. But it contributes to the proton gradient by supplying reducing equivalents resulting from succinate metabolism. The reducing equivalents are then transported through the ubiquinone pool thereby enabling proton extrusion by complex III and IV | Saccharomyces cerevisiae |
| metabolism | succinate dehydrogenase (SDH) is one of the most important enzymes involved in the three cellular processes: glycolysis, the tricarboxylic acid cycle (TCA cycle, Krebs cycle) and oxidative phosphorylation (OXPHOS). SDH, also known as complex II or succinate:ubiquinone oxidoreductase (SQR) is a unique enzyme in four ways: first, it is involved in both the TCA and OXPHOS in mitochondria. Second, all the genes for mitochondrial SDH are nuclear. Third, it is the only membrane-bound component of TCA cycle. Fourth, it is the smallest and the only complex of mitochondrial electron transport chain (ETC) which does not directly extrude protons. But it contributes to the proton gradient by supplying reducing equivalents resulting from succinate metabolism. The reducing equivalents are then transported through the ubiquinone pool thereby enabling proton extrusion by complex III and IV. Succinate is oxidized to fumarate in the TCA cycle by SDHA-B and the electrons derived are transported to ubiquinone (coenzyme Q) and then to complex III. The electrons along the way reduce FAD of SDHA subunit and move through Fe-S clusters in SDHB subunit and then reduce ubiquinone before transfer to complex III | Homo sapiens |
| additional information | SDH complex structure and assembly, detailed overview. Detailed analysis of some proteins that are required for the assembly of SDH e.g. Tcm62p, Flx1, Sdh6 (in yeast), SDH7 (in yeast), and Sdh5 (in yeast). Tcm62 most likely has a chaperone function for SDH, while Sdh5 plays a role in SDH1 flavination. The current model of complex II (succinate dehydrogenase) assembly: Sdh5 bound to Sdh1 facilitates flavination of Sdh1. Sdh5 is then released, while Sdh8 chaperone binds the flavinated Sdh1 to facilitate the dimerization of Sdh1 and Sdh2. Sdh6 and Sdh7 assist in either insertion or retention of [Fe-S] clusters within Sdh2. Sdh2 then forms a dimer with Sdh1, while Sdh6/Sdh7 and Sdh8 are released from Sdh2 and Sdh1, respectively. The dimer is subsequently integrated into the membrane where Sdh3-Sdh4 dimer containing a heme b is formed. There is not much information regarding the formation of Sdh3-Sdh4 dimer. Role of SDH2 in flavination. SDHAF3 together with SDHAF1 is asserted as factors required for maturation of Sdh2/SDHB | Saccharomyces cerevisiae |
| additional information | SDH complex structure and assembly, detailed overview. The SDHA subunit is a flavoprotein containing a covalently bound FAD cofactor and the binding site for dicarboxylates (e.g. succinate). SDHB is an iron-sulfur cluster protein containing three Fe-S clusters. SDHA and SDHB make up the catalytic domain. They extend out into the matrix and constitute the hydrophilic head. SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them. Detailed analysis of some proteins that are required for the assembly of SDH e.g. Tcm62p, Flx1, SDHAF1 or LYRM8, SDHAF3, and SDHAF2. Tcm62 most likely has a chaperone function for SDH. Role of SDHB in flavination. SDHAF3 together with SDHAF1 is asserted as factors required for maturation of Sdh2/SDHB | Homo sapiens |
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Release 2023.1 (January 2023)
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