Original contribution
Permeabilization of the inner mitochondrial membrane by Ca2+ ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria

https://doi.org/10.1016/0891-5849(94)00166-HGet rights and content

Abstract

The extent of swelling undergone by deenergized mitochondria incubated in KC1/sucrose medium in the presence of Ca2+ alone or Ca2+ and t-butyl hydroperoxide decreases by decreasing molecular oxygen concentration in the reaction medium; under anaerobiosis no swelling occurs. This swelling is also inhibited by the presence of exogenous catalase or by the Fe2+ chelator o-phenanthroline in a time-dependent manner. The production of protein thiol cross-linking that leads to the formation of protein aggregates induced by Ca2+ and t-butyl hydroperoxide does not occur when mitochondria are incubated in anaerobic medium or in the presence of o-phenanthroline. In addition, it is also shown that the yield of stable methyl radical adducts, obtained from rat liver mitochondria treated with t-butyl hydroperoxide and the spin trap DMPO, is reduced by addition of EGTA and increases by addition of Ca2+ ions. These data support the hypothesis that Ca2+ ions stimulate electron leakage from the respiratory chain, increasing the mitochondrial production of reactive oxygen species.

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Cited by (231)

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    2020, Molecular Aspects of Medicine
    Citation Excerpt :

    The evidence that cyclosporin A (CsA), a pore-opening inhibitor (Crompton et al., 1988; Broekemeier et al., 1989), prevents cell death under different pathological conditions (Griffiths and Halestrap, 1993; Bernardi et al., 2006) supports the participation of this pore in the pathogenesis of ischaemia/reperfusion, heart and neurodegenerative diseases, traumatic brain injury, muscular dystrophy, inflammation, dyslipidaemias, drug toxicity and ageing (Griffiths and Halestrap, 1993; Bernardi et al., 2006; Halestrap and Pasdois, 2009; Vaseva et al., 2012). The redox hypothesis for mPTP regulation is further supported by the protection against it opening by several antioxidants (Vercesi et al., 2018) or the absence of molecular oxygen (Castilho et al., 1995a). In addition, evidence has shown that exogenous catalase (Valle et al., 1993; Castilho et al., 1995a; Kowaltowski et al., 1996), peroxiredoxin (Kowaltowski et al., 1998) or o-phenanthroline (Castilho et al., 1995a) prevents opening of the mPTP.

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