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

Navratan Bagwan | Zendy; Elena BonzónKulichenko | Zendy; Enrique Calvo | Zendy; Ana Victoria LechugaVieco | Zendy; Spiros Michalakopoulos | Zendy; Marco Trevisán-Herraz | Zendy; Iakes Ezkurdia | Zendy; José Manuel Rodrı́guez | Zendy; Ricardo Magni | Zendy; Ana Latorre | Zendy; José Antonio Enrı́quez | Zendy; Jesús Vázquez | Zendy

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

Author(s) -

Navratan Bagwan,

Elena BonzónKulichenko,

Enrique Calvo,

Ana Victoria LechugaVieco,

Spiros Michalakopoulos,

Marco Trevisán-Herraz,

Iakes Ezkurdia,

José Manuel Rodrı́guez,

Ricardo Magni,

Ana Latorre,

José Antonio Enrı́quez,

Jesús Vázquez

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.05.080

Subject(s) - heteroplasmy , proteome , oxidative phosphorylation , computational biology , proteomics , mitochondrion , biology , shotgun proteomics , microbiology and biotechnology , biochemistry , bioinformatics , mitochondrial dna , gene

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

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