SIRT3 - Sirtuin 3 | Elisa - Clia - Antibody - Protein

Background:

SIRT3, also known as NAD-dependent protein deacetylase sirtuin-3, is a member of the sirtuin family of proteins, which are involved in various cellular processes including metabolism, stress response, and aging. SIRT3 is primarily localized in the mitochondria, the cellular organelles responsible for energy production and other critical metabolic functions. One of the key functions of SIRT3 is its role in regulating mitochondrial metabolism. SIRT3 targets several proteins within the mitochondria, including enzymes involved in oxidative phosphorylation, the citric acid cycle (also known as the Krebs cycle), fatty acid metabolism, and antioxidant defense mechanisms. By deacetylating these target proteins, SIRT3 enhances their activity, leading to increased energy production, improved mitochondrial function, and protection against oxidative stress.SIRT3 has been shown to play a critical role in cellular responses to stress, including oxidative stress and nutrient deprivation. It promotes cell survival under conditions of metabolic stress by regulating mitochondrial metabolism and maintaining cellular energy balance. Additionally, SIRT3 has been implicated in the regulation of apoptosis and the cellular response to DNA damage.

Protein Structure:

• Composition: SIRT3 is composed of 399 amino acids.
• Domains:
• N-terminal Mitochondrial Targeting Sequence: Directs the protein to the mitochondria.
• Catalytic Core: Contains the NAD+-binding site and the deacetylase domain essential for its enzymatic activity.
• C-terminal Domain: Important for protein stability and function.
• Post-translational Modifications: SIRT3 activity is regulated by various post-translational modifications, including phosphorylation and acetylation.

Classification and Subtypes:

• Family: SIRT3 belongs to the sirtuin family, which includes seven members (SIRT1-7) in mammals.
• Subtypes: There are no specific subtypes of SIRT3, but its functions overlap with other mitochondrial sirtuins, particularly SIRT4 and SIRT5.

Function and Biological Significance:

• Mitochondrial Function: SIRT3 regulates mitochondrial biogenesis, dynamics, and respiration by deacetylating and activating key enzymes involved in the electron transport chain and fatty acid oxidation.
• Energy Metabolism: SIRT3 deacetylates and activates enzymes like acetyl-CoA synthetase 2 (AceCS2) and long-chain acyl-CoA dehydrogenase (LCAD), enhancing fatty acid oxidation and ketone body production.
• Antioxidant Defense: SIRT3 promotes the deacetylation and activation of manganese superoxide dismutase (MnSOD), reducing reactive oxygen species (ROS) and protecting cells from oxidative stress.
• Apoptosis Regulation: SIRT3 modulates the intrinsic pathway of apoptosis by deacetylating and regulating proteins such as cyclophilin D, influencing the opening of the mitochondrial permeability transition pore.
• Metabolic Adaptation: SIRT3 is involved in adapting to metabolic stress, such as fasting and calorie restriction, by reprogramming cellular energy metabolism.

Interactions:

• Metabolic Enzymes: SIRT3 interacts with and deacetylates various metabolic enzymes, including AceCS2, LCAD, and isocitrate dehydrogenase 2 (IDH2), enhancing their activities and promoting efficient energy production.
• Antioxidant Proteins: SIRT3 deacetylates and activates MnSOD, a critical enzyme in the mitochondrial antioxidant defense system.
• Apoptotic Regulators: SIRT3 modulates apoptosis by deacetylating proteins involved in the mitochondrial apoptosis pathway, such as cyclophilin D.

Clinical Issues:

• Metabolic Disorders: Dysregulation of SIRT3 is linked to metabolic disorders, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Enhancing SIRT3 activity could be beneficial in these conditions.
• Aging and Longevity: SIRT3 is implicated in the aging process and age-related diseases. It plays a role in promoting healthy aging by enhancing mitochondrial function and reducing oxidative stress.
• Cardiovascular Diseases: SIRT3 is protective against cardiovascular diseases by maintaining mitochondrial integrity and function, reducing oxidative stress, and preventing apoptosis in cardiac cells.
• Cancer: The role of SIRT3 in cancer is complex and context-dependent. It can act as a tumor suppressor by enhancing mitochondrial function and reducing ROS levels. However, in some cancers, SIRT3 may support tumor growth by adapting metabolism to support rapid cell proliferation.

Summary:

Sirtuin 3 (SIRT3) is a mitochondrial NAD+-dependent deacetylase that plays a crucial role in regulating mitochondrial function, energy metabolism, and cellular stress responses. By deacetylating key metabolic enzymes and antioxidant proteins, SIRT3 enhances mitochondrial efficiency, promotes fatty acid oxidation, and reduces oxidative stress. SIRT3 is involved in various physiological processes, including aging, metabolic adaptation, and apoptosis regulation. Dysregulation of SIRT3 is associated with metabolic disorders, aging, cardiovascular diseases, and cancer, making it a potential therapeutic target for these conditions.