Comprehensive Quantification of the Modified Proteome Reveals Oxidative Heart Damage in Mitochondrial Heteroplasmy

• DOI: 10.1016/j.celrep.2018.05.080
• Publication Date: 2018-06-19T14:43:10Z
• Authors: Navratan Bagwan; Elena Bonzon-Kuli...; Enrique Calvo; Ana Victoria Lech...; Spiros Michalakop...; Marco Trevisan-He...; Iakes Ezkurdia; José Manuel Rodrí...; Ricardo Magni; Ana Latorre-Pellicer; José Antonio Enrí...; Jesús Vázquez
• Keywords: Heteroplasmy; Proteome; Shotgun proteomics

Post-translational modifications hugely increase the functional diversity of proteomes. Recent algorithms based on ultratolerant database searching are forging a path to unbiased analysis peptide by shotgun mass spectrometry. However, these approaches identify only one-half modified forms potentially detectable and do not map residue. Moreover, tools for quantitative currently lacking. Here, we present suite that allows comprehensive identification modifications, pinpoints residues, enables their through an integrated statistical model. These developments were used characterize impact mitochondrial heteroplasmy proteome peptidome in several tissues from 12-week-old mice. Our results reveal mainly affects cardiac tissue, inducing oxidative damage proteins phosphorylation system, provide molecular mechanism explaining structural alterations produced heart mitochondria.