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Differentiation potentiates oxidant injury to mitochondria by hydrogen peroxide in Friend's erythroleukemia cells
Author(s) -
Comelli Marina,
Lippe Giovanna,
Mavelli Irene
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00882-5
Subject(s) - oligomycin , atp synthase , hemin , mitochondrion , heme , hydrogen peroxide , oxidative phosphorylation , chemistry , intracellular , biochemistry , microbiology and biotechnology , chemiosmosis , cellular respiration , biophysics , biology , atpase , enzyme
Oxidative damage to mitochondrial functions was investigated upon non‐lethal treatment with H 2 O 2 of Friend's erythroleukemia cells induced to differentiate, in comparison with the parental cell line. Both respiration and maximal ATP synthase capacity were more severely diminished by H 2 O 2 in induced cells. The effects were mediated by intracellular redox‐active iron and OH . radicals. Specifically, the mechanisms of the selective oxidant injury to F 0 F 1 ATP synthase observed in differentiating cells likely involved impairment of F 0 —F 1 coupling sensitive to oligomycin. We suggest a Fenton‐like reaction of H 2 O 2 with iron ions, more available in the differentiating cells, as occurring at the surface and/or in the lipid bulk phase of the inner mitochondrial membrane, thus injuring subunits responsible for the coupling of F 0 F 1 ATP synthase through generation in situ of the actual damaging species. Besides, we propose heme iron as the most likely candidate for such reaction in induced cells actively synthesizing heme. In accordance, pretreatment of uninduced cells with hemin made H 2 O 2 ‐damage qualitatively identical.