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Quantitative Profiling of Protein Carbonylations in Ferroptosis by an Aniline-Derived Probe.
Chen, Ying; Liu, Yuan; Lan, Tong; Qin, Wei; Zhu, Yuntao; Qin, Ke; Gao, Jinjun; Wang, Haobo; Hou, Xiaomeng; Chen, Nan; Friedmann Angeli, Jose Pedro; Conrad, Marcus; Wang, Chu.
Afiliação
  • Friedmann Angeli JP; Institute of Developmental Genetics , Helmholtz Zentrum Munchen , Munchen , Germany.
  • Conrad M; Institute of Developmental Genetics , Helmholtz Zentrum Munchen , Munchen , Germany.
J Am Chem Soc ; 140(13): 4712-4720, 2018 04 04.
Article em En | MEDLINE | ID: mdl-29569437
Ferroptosis is a regulated form of necrotic cell death implicated in carcinogenesis and neurodegeneration that is driven by phospholipid peroxidation. Lipid-derived electrophiles (LDEs) generated during this process can covalently modify proteins ("carbonylation") and affect their functions. Here we report the development of a quantitative chemoproteomic method to profile carbonylations in ferroptosis by an aniline-derived probe. Using the method, we established a global portrait of protein carbonylations in ferroptosis with >400 endogenously modified proteins and for the first time, identified >20 residue sites with endogenous LDE modifications in ferroptotic cells. Specifically, we discovered and validated a novel cysteine site of modification on voltage-dependent anion-selective channel protein 2 (VDAC2) that might play an important role in sensitizing LDE signals and mediating ferroptosis. Our results will contribute to the understanding of ferroptotic signaling and pathogenesis and provide potential biomarkers for ferroptosis detection.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Ferro / Compostos de Anilina Idioma: En Revista: J Am Chem Soc Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Ferro / Compostos de Anilina Idioma: En Revista: J Am Chem Soc Ano de publicação: 2018 Tipo de documento: Article