EC Number   |
Posttranslational Modification |
Reference |
|---|
    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 |
762781 |
| 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 |
762781 |
| 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 |
762781 |
| 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 |
762781 |
| 1.3.5.1 | flavoprotein |
covalent FAD modification of flavoprotein subunit 1 from complex II |
672379 |
| 1.3.5.1 | flavoprotein |
covalent flavinylation of succinate dehydrogenase subunit A requires heat and dicarboxylic acids |
725025 |
| 1.3.5.1 | lipoprotein |
- |
391082 |
| 1.3.5.1 | more |
posttranslational modifications regulate SDH levels by 4 means: phosphorylation, deacetylation, succinylation and propionylation |
762781 |
| 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 |
762781 |
| 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 |
762781 |
