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SIRT4 Research Paper

682 Words3 Pages

Sirtuins (Sir2 proteins) are proteins that exhibit mono-ADP-ribosyltransferase, deacetylase, deacetylase, desuccinylase, demalonylase, demyristoylase, or depalmitoylase activity. They are involved in a broad range of cellular processes which include DNA repair, gene silencing, tumor suppression, life span regulation, apoptosis, inflammation, and stress resistance (low energy/calorie situations). (Michan, 2007) Mammals possess seven cellular regulatory sirtuins (SIRT1-7). SIRT1 partakes in metabolism inflammation in the nucleus and cytoplasm. SIRT2 partakes in cell cycle and tumorigenesis in the cytoplasm. SIRT3 partakes in metabolism in the nucleus and mitochondria. SIRT4 partakes in insulin secretion in the mitochondria. SIRT5 partakes in …show more content…

Typically, cells opt for aerobic respiration of glucose because of higher ATP yield and will only perform anaerobic respiration under conditions of low nutrient availability or high stress (hypoxia). In SIRT6 deficient cells, lactate glycolysis persists, indicating that the cell switches from growth mode to survival mode; there is an increase in glucose uptake and lactate production and decrease in oxygen consumption and ATP production. (Zhong, Mostoslavsky 2010) SIRT6 deficiency promotes pyruvate conversion to lactate and blocks mitochondrial oxidative phosphorylation …show more content…

In the presence of SIRT6, expression of lactate dehydrogenase, triose phosphate isomerase (Tpi), aldolase, Glut1, phosphofructokinase-1 (Pfk-1), and Pyruvate Dehydrogenase Kinase genes (Pdk1 and Pdk4) is silenced.
SIRT6 also interacts with Hypoxia Inducible Transcription factor 1a (Hif1a), another important glycolytic regulator and key mediator in cell adaptation to stress. Hif1a modulates multiple genes to activate glycolysis and repress mitochondrial respiration. (Zhong, D'Urso, et all, 2010) Under conditions of normal glucose availability, SIRT6 functions as a repressor of Hif1a, diverting pyruvate towards the citric acid cycle for efficient ATP production. SIRT6 binds to Hif1a, follows it to its target genes where it deacetylates gene promoters, and represses expression.
To sum it up, SIRT6 influences glucose metabolism because when SIRT6 is present, the cell undergoes aerobic respiration in the mitochondria because Hif1a, a glycolysis activator and mitochondrial respiration repressor, is repressed and glycolytic genes blocking mitochondrial respiration are silenced. When there is an SIRT6 deficiency, the opposite occurs; there is increased glycolysis and diminished mitochondrial

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