Cardiolipin interactions with cytochrome c increase tyrosine nitration yields and site-specificity.

Autor: Demicheli V; Departamento de Bioquímica, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Tomasina F; Departamento de Bioquímica, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Sastre S; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Zeida A; Departamento de Bioquímica, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Tórtora V; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Lima A; Institut Pasteur de Montevideo, Uruguay; Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay., Batthyány C; Institut Pasteur de Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay., Radi R; Departamento de Bioquímica, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Electronic address: rradi@fmed.edu.uy.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2021 May 30; Vol. 703, pp. 108824. Date of Electronic Publication: 2021 Mar 04.
DOI: 10.1016/j.abb.2021.108824
Abstrakt: The interaction between cytochrome c and cardiolipin is a relevant process in the mitochondrial redox homeostasis, playing roles in the mechanism of electron transfer to cytochrome c oxidase and also modulating cytochrome c conformation, reactivity and function. Peroxynitrite is a widespread nitrating agent formed in mitochondria under oxidative stress conditions, and can result in the formation of tyrosine nitrated cytochrome c. Some of the nitro-cytochrome c species undergo conformational changes at physiological pH and increase its peroxidase activity. In this work we evaluated the influence of cardiolipin on peroxynitrite-mediated cytochrome c nitration yields and site-specificity. Our results show that cardiolipin enhances cytochrome c nitration by peroxynitrite and targets it to heme-adjacent Tyr67. Cytochrome c nitration also modifies the affinity of protein with cardiolipin. Using a combination of experimental techniques and computer modeling, it is concluded that structural modifications in the Tyr67 region are responsible for the observed changes in protein-derived radical and tyrosine nitration levels, distribution of nitrated proteoforms and affinity to cardiolipin. Increased nitration of cytochrome c in presence of cardiolipin within mitochondria and the gain of peroxidatic activity could then impact events such as the onset of apoptosis and other processes related to the disruption of mitochondrial redox homeostasis.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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