title: Microcin J25 triggers cytochrome c release through irreversible damage of mitochondrial proteins and lipids.
abstract: We previously showed that the antimicrobial peptide microcin J25 induced the over-production of reactive oxygen species with the concomitant release of cytochrome c from rat heart mitochondria via the opening of the mitochondrial permeability transition pore. Here, we were able to demonstrate that indeed, as a consequence of the oxidative burst, MccJ25 induces carbonylation of mitochondrial proteins, which may explain the irreversible inhibition of complex III and the partial inhibition of superoxide dismutase and catalase. Moreover, the peptide raised the levels of oxidized membrane lipids, which triggers the release of cytochrome c. From in silico analysis, we hypothesize that microcin would elicit these effects through interaction with heme c1 at mitochondrial complex III. On the other hand, under an excess of l-arginine, MccJ25 caused nitric oxide overproduction with no oxidative damage and a marked inhibition in oxygen consumption. Therefore, a beneficial anti-oxidative activity could be favored by the addition of l-arginine. Conversely, MccJ25 pro-oxidative-apoptotic effect can be unleashed in either an arginine-free medium or by suppressing the nitric oxide synthase activity.
authors.affiliation: Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional de Tucumán), Instituto de Química Biológica Dr. Bernabe Bloj, Chacabuco 461, San Miguel de Tucumán 4000, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Niklison-Chirou
authors.forename: Fernando
authors.initials: F
authors.lastname: Dupuy
authors.forename: Liliana B
authors.initials: LB
authors.lastname: Pena
authors.forename: Susana M
authors.initials: SM
authors.lastname: Gallego
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Barreiro-Arcos
authors.forename: Cesar
authors.initials: C
authors.lastname: Avila
authors.forename: Clarisa
authors.initials: C
authors.lastname: Torres-Bugeau
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Arcuri
authors.forename: Augusto
authors.initials: A
authors.lastname: Bellomio
authors.forename: Carlos
authors.initials: C
authors.lastname: Minahk
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Morero
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001430:Bacteriocins / Q000494:pharmacology*; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000475:Alkenes; D001430:Bacteriocins; D004791:Enzyme Inhibitors; D008563:Membrane Lipids; D024101:Mitochondrial Proteins; C020411:microcin; D009569:Nitric Oxide; D045304:Cytochromes c