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

详细信息    查看全文

• 作者：Thiago C. Genaro-Mattos ; Patricia P. Appolin谩rio ; Katia C. U. Mugnol ; Carlos Bloch Jr. ; Iseli L. Nantes ; Paolo Di Mascio ; Sayuri Miyamoto
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：October 21, 2013
• 年：2013
• 卷：26
• 期：10
• 页码：1536-1544
• 全文大小：399K
• 年卷期：v.26,no.10(October 21, 2013)
• ISSN：1520-5010

文摘

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鈥損rotein and protein鈥搈embrane 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.