Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. J Biol Chem 2014 May 23;289(21):14719-30
Date
04/10/2014Pubmed ID
24713701Pubmed Central ID
PMC4031527DOI
10.1074/jbc.M113.525790Scopus ID
2-s2.0-84901407632 (requires institutional sign-in at Scopus site) 76 CitationsAbstract
Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. Furthermore, mitochondrial morphology was altered in these cells. Both cellular respiration and glycolysis were reduced in OGT/OGA-overexpressing cells. These data demonstrate that alterations in O-GlcNAc cycling profoundly affect energy and metabolite production.
Author List
Tan EP, Villar MT, E L, Lu J, Selfridge JE, Artigues A, Swerdlow RH, Slawson CAuthor
Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylglucosamineCell Line, Tumor
Citric Acid Cycle
Electron Transport
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glycolysis
Humans
Immunoblotting
Mass Spectrometry
Microscopy, Electron
Mitochondria
Mitochondrial Proteins
N-Acetylglucosaminyltransferases
Proteomics
beta-N-Acetylhexosaminidases
