Adipose Carbonylation and Mitochondrial Dysfunction

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

“…Proteomic evaluation of in vitro-modified histones revealed multiple types of adducts on all core histones, but the majority of identified sites were Michael adducts (Figure 3C,D). These results are consistent with previous work indicating that Schiff base modification is labile and reversible, while Michael adducts are stable and non-reversible [11].…”

“…In vitro modification led to the robust modification of all core histones at the same rate, indicating that there is not a detectable site preference for 4-HNE modification in vitro (Figure 3A). 4-HNE modification of proteins most commonly occurs as either a Michael adduct on side chains of lysine, histidines, and cysteines or as a Schiff base on lysine residues [11]. Proteomic evaluation of in vitro-modified histones revealed multiple types of adducts on all core histones, but the majority of identified sites were Michael adducts (Figure 3C,D).…”

“…Hydroxyl radicals attack the acyl chains of polyunsaturated lipids (either free fatty acids, triglycerides or membrane phospholipids) ultimately leading to the formation of highly reactive, diffusible lipid aldehydes. These aldehydes, such as 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE), are subject to nucleophilic attack by the side chains of lysine, cysteine, and histidine residues, resulting in covalent lipid adducts [11]. Although the modification is chemical, it is clear that specific proteins are modified [10][11][12][13][14][15].…”

“…These aldehydes, such as 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE), are subject to nucleophilic attack by the side chains of lysine, cysteine, and histidine residues, resulting in covalent lipid adducts [11]. Although the modification is chemical, it is clear that specific proteins are modified [10][11][12][13][14][15]. In addition, a recent report suggests that de-carbonylation may be an enzymatically-driven process and that the steady state level of carbonylation is driven by the balance between chemical modification and enzymatic de-modification [12].…”