Abstract
O-linked N-acetylglucosamine (O-GlcNAc) is a posttranslational modification that is increasingly recognized as a signal transduction mechanism. Unlike other glycans, O-GlcNAc is a highly dynamic and reversible process that involves the addition and removal of a single N-acetylglucosamine molecule to Ser/Thr residues of proteins. UDP-GlcNAc—the direct substrate for O-GlcNAc modification—is controlled by the rate of cellular metabolism, and thus O-GlcNAc is dependent on substrate availability. Serving as a feedback mechanism, O-GlcNAc influences the regulation of insulin signaling and glucose transport. Besides nutrient sensing, O-GlcNAc was also implicated in the regulation of various physiological and pathophysiological processes. Due to improvements of mass spectrometry techniques, more than one thousand proteins were detected to carry the O-GlcNAc moiety; many of them are known to participate in the regulation of metabolites, ions, or protein transport across biological membranes. Recent studies also indicated that O-GlcNAc is involved in stress adaptation; overwhelming evidences suggest that O-GlcNAc levels increase upon stress. O-GlcNAc elevation is generally considered to be beneficial during stress, although the exact nature of its protective effect is not understood. In this review, we summarize the current data regarding the oxidative stress-related changes of O-GlcNAc levels and discuss the implications related to membrane trafficking.
Highlights
The function and impact of protein O-linked Nacetylglucosamine (O-GlcNAc) modification are very complex and only partially discovered despite almost 1300 scientific studies were published in the last 30 years
We summarize our current understanding of the intracellular process called OGlcNAc modification, its adaptive response regarding oxidative stress, and its influence on membrane traffic, including glucose and ion transport and synaptic, nuclear, and mitochondrial transport
Considering that this function is an important part of the cellular metabolism, it is plausible that O-GlcNAc modification could regulate mitochondrial activity through voltage-dependent anion channels (VDACs)
Summary
The function and impact of protein O-linked Nacetylglucosamine (O-GlcNAc) modification are very complex and only partially discovered despite almost 1300 scientific studies were published in the last 30 years. O-GlcNAc directly influences various regulatory systems, such as the transcriptional machinery, protein synthesis, trafficking and degradation, and regulation of glucose uptake [7, 8]. Despite difficulties in discerning cause and effect (e.g., malignant cells may develop altered metabolic rate and/or O-GlcNAc levels independently), it appears that besides metabolic challenges, regular cellular events such as mitosis, cell differentiation, and response to a hormonal signal or cell-cell adhesion may directly influence O-GlcNAc modifications on proteins [9,10,11,12,13]. The most comprehensive data available were provided by studies done on cardiomyocytes under ischemic or oxidative conditions The majority of these studies showed that elevation of O-GlcNAc prevented or at Oxidative Medicine and Cellular Longevity least ameliorated the damage caused by the stress. We summarize our current understanding of the intracellular process called OGlcNAc modification, its adaptive response regarding oxidative stress, and its influence on membrane traffic, including glucose and ion transport and synaptic, nuclear, and mitochondrial transport
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