Exploiting proteomics in the discovery of drugs that target mitochondrial oxidative damage.
To understand how oxidative stress contributes to aging and age-related diseases and to better evaluate the therapeutic effect of antioxidant drugs, it would be highly desirable to have a comprehensive and detailed readout of the types of oxidative damage that occur to proteins at a global or proteome level. In this Perspective, I examine how proteomics, defined here as the science of examining all proteins in an organelle, cell, or tissue in the context of biological phenomena, can be used to provide molecular details of mitochondrial protein oxidative damage. Specifically, I discuss approaches that combine knowledge of the mitochondrial proteome with newer mass spectrometry-based techniques that are capable of identifying proteins and sites of oxidative modification in a high-throughput manner.
Gibson
Bradford W
BW
Buck Institute for Age Research, Novato, CA 94945, USA. bgibson@buckinstitute.org
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins