Summary of SIRT3
SIRT3 is a mitochondrial protein and has also been studied in regards to longevity and metabolic syndrome. It is involved in controlling reactive oxygen species in the cell. Higher levels of SIRT3 are connected to longevity . SIRT3 is also involved in metabolism, and a study with mice lacking SIRT3 had greater obesity and insulin resistance on a high fat diet. Reduction of SIRT3 function was found to lead to mitochondrial dysfunction and metabolic syndrome (R). Lower SIRT3 is also thought to be a causal factor for pulmonary hypertension (R).
The Function of SIRT3
NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5O. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.
Protein names
Recommended name:
NAD-dependent protein deacetylase sirtuin-3, mitochondrialAlternative name(s):
hSIRT3Regulatory protein SIR2 homolog 3
SIR2-like protein 3
- RS11246020 (SIRT3) ??
- RS11555236 (SIRT3) ??
- RS7104764 (SIRT3) ??
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Top Gene-Substance Interactions
SIRT3 Interacts with These Diseases
| Disease | Score |
Fixes
Read/Fix: About SIRT3 and Natural Ways to Increase It
- Calorie restriction (R)
- Exercise (R)
- Nicotinamide Riboside/ Niagen NAD (R),
- PQQ (R)
- R-Lipoic Acid (R),
- Resveratrol (R),
- Berberine (R),
- EGCG (R, R2) “ but EGCG decreases SIRT3 in cancer cells (good) (R)
- Bitter Melon (R),
- Oroxylin A- Skullcap (R),
- Leucine (R),
- HMB (R),
- ALCAR (R),
Fixes Advanced
Other supplements/phytochemicals that increase SIRT3:
- Hydrogen Peroxide (R)
- Dan shen (Salvianolic acid A) (R),
- Kaempferol (R)
- Areca nut (keratinocytes) (R)
- Caffeic acid prevented decreased SIRT3 in liver injury model (R) Chlorogenic acid/Green Coffee Extract also has caffeic acid.
Pathways that increase SIRT3: Estrogen/Estrogen related receptor alpha (R), PGC-1a (R), PPARa (R), Hydrogen Sulfide (R), You want to be careful about things that inhibit SIRT3. What Inhibits SIRT3: A ketogenic diet decreases SIRT3 in mice (R). Metformin decreases SIRT3 in the liver (R).
Substances That Increase SIRT3
| Substances | Interaction | Organism | Category |
Substances That Decrease SIRT3
| Substances | Interaction | Organism | Category |
Advanced Summary
Read: Waking Up With SIRT3 Genes: Lose Weight and Gain Energy SIRT3 is a mitochondrial protein and has also been studied in regards to longevity and metabolic syndrome. It is involved in controlling reactive oxygen species in the cell. Higher levels of SIRT3 are connected to longevity . SIRT3 is also involved in metabolism, and a study with mice lacking SIRT3 had greater obesity and insulin resistance on a high fat diet. Reduction of SIRT3 function was found to lead to mitochondrial dysfunction and metabolic syndrome (R). Lower SIRT3 is also thought to be a causal factor for pulmonary hypertension (R). --------------------------------------------------------------------------------------
One major function of SIRT3 is regulation of mitochondrial electron transport chain activity to increase energy production, particularly from fat.
SIRT3 is important for activating various enzyme (e.g. LCAD) that break down and burn fat for energy. Simultaneously, SIRT3 decreases carb metabolism (R).
SIRT3 increases increase acetyl-coa (by increasing acetyl-CoA synthetase 2), which is the fuel for the Kreb cycle (R).
Additionally, SIRT3 directly stimulates the Krebs cycle to increase energy production (especially the conversion of isocitrate to -ketoglutarate by increasing IDH2 activity) (R).
SIRT3 promotes mitochondrial function by enhancing the activity of the first (NDUFS1&9) and second complexes (Sdha) in the mitochondrial electron transport chain. It might also stimulate the fifth complex (R).
Mice without SIRT3 show reduced ATP levels at baseline and during cellular stress (R).
SIRT3 increases the activity of SOD2 (MnSOD), reducing oxidative and radiation stress in mice, and this is one mechanism by which calorie restriction helps combat oxidative stress (R).
SIRT3 is important for getting into ketosis (SIRT3-deficient mice are unable to produce normal levels of ketone bodies upon fasting) (R).
SIRT3 results in increased NADPH levels, increased reduced glutathione in mitochondria (means its charged and ready to combat free radicals), and decreased DNA damage in the ear (cochlea) and in other tissues.
High levels of SIRT3 in mice inhibits hypoxia inducible factor, which suppresses tumor growth (R).
SIRT3 decreases the synthesis of proteins in the mitochondria (by decreasing the activity of the ribosomal protein MRPL10) (R).
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed.
Gene Pathways:
Cofactor:
Binds 1 zinc ion per subunit.
Molecular Function:
- Nad+ Adp-Ribosyltransferase Activity
- Nad+ Binding
- Nad-Dependent Histone Deacetylase Activity (H3-K14 Specific)
- Zinc Ion Binding
Biological Processes:
- Aerobic Respiration
- Aging
- Mitochondrion Organization
- Negative Regulation Of Erk1 And Erk2 Cascade
- Negative Regulation Of Peptidyl-Lysine Acetylation
- Negative Regulation Of Reactive Oxygen Species Metabolic Process
- Peptidyl-Lysine Deacetylation
- Positive Regulation Of Insulin Secretion
- Protein Adp-Ribosylation
- Protein Deacetylation