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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Covalent Binding and Anchoring of Cytochrome c to Mitochondrial Mimetic Membranes Promoted by Cholesterol Carboxyaldehyde

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Autor(es):
Genaro-Mattos, Thiago C. [1] ; Appolinario, Patricia P. [1] ; Mugnol, Katia C. U. [2] ; Bloch, Jr., Carlos [3] ; Nantes, Iseli L. [2] ; Di Mascio, Paolo [1] ; Miyamoto, Sayuri [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo - Brazil
[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
[3] Embrapa Recursos Genet & Biotecnol, Lab Espectrometria Massas, Brasilia, DF - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Chemical Research in Toxicology; v. 26, n. 10, p. 1536-1544, OCT 2013.
Citações Web of Science: 8
Resumo

Mitochondrial cholesterol has been reported to be increased under specific pathological conditions associated with enhanced oxidative stress parameters. In this scenario, cholesterol oxidation would be increased, leading to the production of reactive aldehydes, including cholesterol carboxyaldehyde (ChAld). By using SDS micelles as a mitochondrial mimetic model, we have demonstrated that ChAld covalently modifies cytochrome c (cytc), a protein known to participate in electron transport and apoptosis signaling. This mimetic model, induces changes in cytc structure in the same way as mitochondrial membranes do. Tryptic digestion of the cytc-ChAld adduct followed by MALDI-TOF/TOF analyses revealed that modifications occur at Lys residues (K22) localized at cytc site L, a site involved in protein-protein and protein-membrane interactions. Interestingly, ChAld ligation prevented cytc detachment from liposomes even under high ionic strength conditions. Overall, it can be concluded that ChAld ligation to Lys residues at site L creates a hydrophobic tail at cytc, which promotes cytc anchoring to the membrane. Although not investigated in detail in this study, cytc adduction to cholesterol derived aldehydes could have implications in cytc release from mitochondria under apoptotic stimuli. (AU)

Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs