Early modification of cytochrome c by hydrogen peroxide triggers its fast degradation

0548122 - MBÚ 2022 RIV NL eng J - Journal Article
Tomášková, N. - Novák, Petr - Kožár, T. - Petrenčáková, M. - Jančura, D. - Yassaghi, Ghazaleh - Man, Petr - Sedlák, E.
Early modification of cytochrome c by hydrogen peroxide triggers its fast degradation.
International Journal of Biological Macromolecules. Roč. 174, MAR 31 2021 (2021), s. 413-423. ISSN 0141-8130. E-ISSN 1879-0003
R&D Projects: GA ČR(CZ) GA19-16084S; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LQ1604
EU Projects: European Commission(XE) 731077 - EU_FT-ICR_MS
Research Infrastructure: CIISB II - 90127
Institutional support: RVO:61388971
Keywords : Pseudo-peroxidases * Oxidative damage * Reactive oxygen species * Protein channels * Suicide inactivation
OECD category: Biochemistry and molecular biology
Impact factor: 8.025, year: 2021
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0141813021002373?via%3Dihub

Cytochrome c (cyt c), in addition to its function as an electron shuttle in respiratory chain, is able to perform as a pseudo-peroxidase with a critical role during apoptosis. Incubation of cyt c with an excess of hydrogen peroxide leads to a suicide inactivation of the protein, which is accompanied by heme destruction and covalent modification of numerous amino add residues. Although steady-state reactions of cyt c with an excess of hydrogen peroxide represent non-physiological conditions, they might be used for analysis of the first-modified amino add in in vivo. Here, we observed oxidation of tyrosine residues 67 and 74 and heme as the first modifications found upon incubation with hydrogen peroxide. The positions of the oxidized tyrosines suggest a possible migration pathway of hydrogen peroxide-induced radicals from the site of heme localization to the protein surface. Analysis of a size of folded fraction of cyt c upon limited incubation with hydrogen peroxide indicates that the early oxidation of amino acids triggers an accelerated destruction of cyt c. Position of channels from molecular dynamics simulation structures of cyt c points to a location of amino acid residues exposed to reactive oxidants that are thus more prone to covalent modification. (C) 2021 Elsevier B.V. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0324235