Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6576
Título
Comprehensive Quantification of the Modified Proteome Reveals Oxidative Heart Damage in Mitochondrial Heteroplasmy
Autor(es)
Bagwan, Navratan CNIC | Bonzon-Kulichenko, Elena CNIC | Calvo, Enrique CNIC | Lechuga-Vieco, Ana V. CNIC | Michalakopoulos, Spiros CNIC | Trevisan-Herraz, Marco CNIC | Ezkurdia, Iakes CNIC | Rodriguez, Jose Manuel CNIC | Magni, Ricardo CNIC | Latorre-Pellicer, Ana CNIC | Enriquez, Jose Antonio CNIC | Vazquez, Jesus CNIC
Fecha de publicación
2018
Cita
Cell Rep. 2018; 23(12):3685-3697
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
SPECTROMETRY-BASED PROTEOMICS | TANDEM MASS-SPECTROMETRY | DATABASE SEARCH TOOL | POSTTRANSLATIONAL MODIFICATIONS | PEPTIDE IDENTIFICATION | SHOTGUN PROTEOMICS | QUANTITATIVE PROTEOMICS | PHOSPHORYLATION | PHOSPHOPROTEOME | EXPRESSION
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DOI
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