biostudies-literatureZhang YNational Natural Science Foundation of China66https://www.ebi.ac.uk/biostudies/studies/S-EPMC6347623biostudies-literatureUnknown10(2)Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose revealed hyperacetylation of enzymes involved in fatty acid β-oxidation (FAO), including trifunctional enzyme subunit alpha (ECHA). Acetylation decreased the protein stability of ECHA and its ability to promote FAO. The overexpression of SIRT3, a major mitochondrial deacetylase, prevented the degradation of ECHA via decreasing its acetylation level in β-cells. SIRT3 expression was upregulated in rat islets upon exposure to low glucose or fasting. SIRT3 overexpression in islets maCell death & diseaseThe pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function.PMC634762381270910811707208157069381370876Liu YZhou LZhang YBai MZhou FZhang LWang XZhu QNing GBi YfalseThe pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function.Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose revealed hyperacetylation of enzymes involved in fatty acid β-oxidation (FAO), including trifunctional enzyme subunit alpha (ECHA). Acetylation decreased the protein stability of ECHA and its ability to promote FAO. The overexpression of SIRT3, a major mitochondrial deacetylase, prevented the degradation of ECHA via decreasing its acetylation level in β-cells. SIRT3 expression was upregulated in rat islets upon exposure to low glucose or fasting. SIRT3 overexpression in islets ma2019-01-01T00:00:00Z2019 Jan2025-05-29T22:27:59.623Z2025-05-29T22:27:59.623ZS-EPMC63476233068385010.1038/s41419-019-1349-z