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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 7
[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
Total Affiliations: 3
Document type: Journal article
Source: Chemical Research in Toxicology; v. 26, n. 10, p. 1536-1544, OCT 2013.
Web of Science Citations: 8

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)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC