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

Bagwan N, Bonzon-Kulichenko E, Calvo E, Lechuga-Vieco AV, Michalakopoulos S, Trevisan-Herraz M, Ezkurdia I, Rodríguez JM, Magni R, Latorre-Pellicer A, Enríquez JA, Vázquez J

https://www.sciencedirect.com/science/article/pii/S2211124718308611?via%3Dihub

• Mass spectrometry is a powerful tool for proteomics. A large proportion of unassigned spectra are thought to arise from peptides containing sequence variants or unknown chemical/post-translational modifications.
• The authors present a suite of bioinformatics tools which extend the coverage which can be attained from mass spectrometry, which allow the location of the modified residues and quantitative analysis of post-translational modification.
• The authors test their approach in the context of mitochondrial heteroplasmy in 12 week old (i.e. young) mice carrying two non-pathological mtDNA variants. The first mtDNA variant is the original variant which co-evolved with the nucleus (C57BL/6J). The second mtDNA variant is NZB.
• The authors found evidence of protein alterations in the heart of heteroplasmic mice which were consistent with mitochondrial dysfunction. 
• The alterations in heteroplasmic mice were consistent with the decreased ATP synthesis and the abnormal increase in phosphocreatine/ATP ratio in the heart, shift to glycolysis, and with the increase in plasma creatine kinase which have been observed in this animal model (unpublished data).
• The authors detected signs of inflammation in the liver of heteroplasmic mice with aging; however, heteroplasmy mainly produces oxidative modifications of OXPHOS proteins in the heart, at this age.