Open AccessComparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts
Author(s) -
Junfeng Ma,
P. S. Banerjee,
Stephen A. Whelan,
Ting Liu,
An-Chi Wei,
Genaro A. Ramírez-Correa,
Mark E. McComb,
Catherine E. Costello,
Brian O’Rourke,
Anne M. Murphy,
Gerald W. Hart
Publication year - 2016
Publication title -
journal of proteome research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 161
eISSN - 1535-3907
pISSN - 1535-3893
DOI - 10.1021/acs.jproteome.6b00250
Subject(s) - diabetic cardiomyopathy , threonine , serine , mitochondrion , proteomics , diabetes mellitus , biology , microbiology and biotechnology , cytoplasm , biochemistry , cardiomyopathy , phosphorylation , chemistry , medicine , endocrinology , heart failure , gene
O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy.