The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function.

Abstract:

: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 markedly decreased palmitate-potentiated insulin secretion, whereas islets from SIRT3 knockout mice secreted more insulin, with an opposite action on FAO. ECHA overexpression partially reversed SIRT3 deficiency-elicited insulin hypersecretion. Our study highlights the potential role of protein acetylation in insulin secretion.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Zhang Y,Zhou F,Bai M,Liu Y,Zhang L,Zhu Q,Bi Y,Ning G,Zhou L,Wang X

doi

10.1038/s41419-019-1349-z

subject

Has Abstract

pub_date

2019-01-25 00:00:00

pages

66

issue

2

issn

2041-4889

pii

10.1038/s41419-019-1349-z

journal_volume

10

pub_type

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