Mitochondrial lysine deacetylation promotes energy metabolism and calcium signaling in insulin-secreting cells

What is it about?

The hormone insulin is secreted from pancreatic beta-cells to lower blood glucose. Impairment of insulin secretion leads to hyperglycemia and the development of Type 2 diabetes. When glucose in the blood rises, pancreatic beta-cells are activated by the nutrient. This activation requires metabolism of glucose, which is oxidized to water and CO2 inside mitochondria. Mitochondria are an energy producing organelle and in the beta-cell generate signals that lead to insulin secretion. Mitochondria are therefore an essential player linking glucose sensing and insulin secretion. The primary function of mitochondria is to consume oxygen to generate energy in the form of ATP. In the beta-cell, an increase in the cellular ATP level also promotes insulin secretion. Mitochondrial activity is regulated at multiple levels and each of these regulatory processes influences insulin secretion. Here we observe that the modification of mitochondrial proteins by lysine acetylation is crucial for the control of mitochondrial ATP production. In cells lacking the enzyme SIRT3, which deacetylates proteins, exaggerated levels of lysine acetylated proteins are observed. This may negatively affects the function of mitochondrial proteins. Unlike normal insulin secreting cells, the cells lacking SIRT3 are over-activated at low glucose concentrations and very poorly respond when stimulated with glucose. Our results demonstrate the importance of mitochondrial lysine acetylation in the processes linking glucose metabolism to insulin secretion. Alterations of lysine acetylation in mitochondria may therefore influence insulin secretion and as a result affect the development of Type 2 diabetes.

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