Covalent binding and anchoring of cytochrome c to mitochondrial mimetic membranes promoted by cholesterol carboxyaldehyde

Thiago C. Genaro-Mattos, Patricia P. Appolinário, Katia C.U. Mugnol, Carlos Bloch, Iseli L. Nantes, Paolo Di Mascio, Sayuri Miyamoto

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1536-1544
Number of pages9
JournalChemical Research in Toxicology
Volume26
Issue number10
DOIs
StatePublished - Nov 4 2013

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Mitochondrial Membranes
Cytochromes c
Cholesterol
Membranes
Aldehydes
Ligation
Proteins
Mitochondria
Oxidative stress
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Micelles
Electron Transport
Ionic strength
Liposomes
Osmolar Concentration
Digestion
Membrane Proteins
Oxidative Stress
Apoptosis
Oxidation

ASJC Scopus subject areas

  • Toxicology

Cite this

Covalent binding and anchoring of cytochrome c to mitochondrial mimetic membranes promoted by cholesterol carboxyaldehyde. / Genaro-Mattos, Thiago C.; Appolinário, Patricia P.; Mugnol, Katia C.U.; Bloch, Carlos; Nantes, Iseli L.; Di Mascio, Paolo; Miyamoto, Sayuri.

In: Chemical Research in Toxicology, Vol. 26, No. 10, 04.11.2013, p. 1536-1544.

Research output: Contribution to journalArticle

Genaro-Mattos, Thiago C. ; Appolinário, Patricia P. ; Mugnol, Katia C.U. ; Bloch, Carlos ; Nantes, Iseli L. ; Di Mascio, Paolo ; Miyamoto, Sayuri. / Covalent binding and anchoring of cytochrome c to mitochondrial mimetic membranes promoted by cholesterol carboxyaldehyde. In: Chemical Research in Toxicology. 2013 ; Vol. 26, No. 10. pp. 1536-1544.
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