Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective

Proteins can become oxidatively modified in many different ways, either by direct oxidation of amino acid side chains and protein backbone or indirectly by conjugation with oxidation products of polyunsaturated fatty acids and carbohydrates. While reversible oxidative modifications are thought to be relevant in physiological processes, irreversible oxidative modifications are known to contribute to cellular damage and disease. The most well-studied irreversible protein oxidation is carbonylation. In this work we first examine how protein carbonylation occurs via metal-catalyzed oxidation (MCO) in vivo and in vitro with an emphasis on cellular metal ion homeostasis and metal binding. We then review proteomic methods currently used for identifying carbonylated proteins and their sites of modification. Finally, we discuss the identified carbonylated proteins and the pattern of carbonylation sites in relation to cellular metabolism using the mitochondrion as a case story.

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► TProtein carbonylation is an irreversible oxidative modification that can lead to changes in protein structure and function.
► Metal-catalyzed oxidation may be the main mechanism of protein carbonylation in vivo.
► It is difficult to identify carbonylation sites because of the large number of possible co-existing oxidative modifications.
► To date 450 protein carbonylation sites have been identified and they have a tendency to cluster in RKPT-rich regions.
► Mitochondria are major sites of ROS production and carbonylation. The regulation of these processes is poorly understood.