title: Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts.
abstract: 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.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Ma
authors.forename: Partha
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Whelan
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Wei
authors.forename: Genaro
authors.initials: G
authors.lastname: Ramirez-Correa
authors.affiliation: Department of Biochemistry, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: McComb
authors.affiliation: Department of Biochemistry, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.forename: Anne
authors.initials: A
authors.lastname: Murphy
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D058065:Diabetic Cardiomyopathies / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: D024101:Mitochondrial Proteins; D000117:Acetylglucosamine
keywords: O-GlcNAcome; O-GlcNAcylation; diabetic cardiomyopathy; mass spectrometry; mitochondria; proteomics; pyruvate dehydrogenase