A Chemical Glycoproteomics Platform Reveals O-GlcNAcylation of Mitochondrial Voltage-Dependent Anion Channel 2

Krishnan K. Palaniappan; Matthew J. Hangauer; Timothy J. Smith; Brian P. Smart; Austin A. Pitcher; Emily H. Cheng; Carolyn R. Bertozzi; Michael Boyce

doi:10.1016/j.celrep.2013.08.048

Cell Reports (Oct 2013)

A Chemical Glycoproteomics Platform Reveals O-GlcNAcylation of Mitochondrial Voltage-Dependent Anion Channel 2

Krishnan K. Palaniappan,
Matthew J. Hangauer,
Timothy J. Smith,
Brian P. Smart,
Austin A. Pitcher,
Emily H. Cheng,
Carolyn R. Bertozzi,
Michael Boyce

Affiliations

Krishnan K. Palaniappan: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA
Matthew J. Hangauer: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA
Timothy J. Smith: Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA
Brian P. Smart: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA
Austin A. Pitcher: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA
Emily H. Cheng: Human Oncology and Pathogenesis Program and Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
Carolyn R. Bertozzi: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA
Michael Boyce: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA

DOI: https://doi.org/10.1016/j.celrep.2013.08.048
Journal volume & issue: Vol. 5, no. 2
pp. 546 – 552

Abstract

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Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is a critical cell signaling modality, but identifying signal-specific O-GlcNAcylation events remains a significant experimental challenge. Here, we describe a method for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated proteins and use it to identify the mitochondrial voltage-dependent anion channel 2 (VDAC2) as an O-GlcNAc substrate. VDAC2−/− cells resist the mitochondrial dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating a functional connection between O-GlcNAc signaling and mitochondrial physiology through VDAC2. More broadly, our method will enable the discovery of signal-specific O-GlcNAcylation events in a wide array of experimental contexts.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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