title: Effects of oxygen and antioxidants on the mitochondrial Ca-retention capacity.
abstract: 2-Oxoglutarate-supported rat liver mitochondria were loaded with moderate amounts of calcium and submitted to O2 deprivation and reoxygenation. In the presence of acetoacetate, anaerobic energy production maintained Ca2+ retention by mitochondria during the anoxia period unless the Pi concentration of the incubation solution was raised to 4-6 mM. Acetoacetate prompted Ca2+ release from O2-deprived mitochondria at elevated Pi levels, presumably due to occurrence of a permeability transition of the inner membrane. Providing 3-hydroxybutyrate and malate, together with acetoacetate, was found to delay the permeability transition until O2 was reintroduced, i.e., O2 triggered a paradoxical release of Ca2+ from mitochondria under these conditions. Whether initiated by O2 in the presence of Pi or by Pi under aerobic conditions, Ca2+ release was initially activated and subsequently inhibited or reversed in the presence of alpha-tocopherol (10-90 mumol.g protein-1). Similar effects were exerted by alpha-tocopherol during Pi-induced Ca2+ release from oligomycin-treated mitochondria supported by succinate (+ rotenone). In addition, the permeability transition was delayed by retinol (3-30 mumol.g protein-1) while beta-carotene, ubiquinone, and water-soluble antioxidants, including Trolox C, were ineffective. Other observations suggest that the Ca(2+)-releasing and/or -retaining effects of alpha-tocopherol and retinol may be independent from pro- and/or antioxidant activities. Effects resembling those of alpha-tocopherol were exerted by alpha-tocopherol succinate, which is devoid of antioxidant activity. Our data indicate that the permeability transition of Ca(2+)-loaded liver mitochondria may be triggered by O2, in the presence of ketone bodies, and affected by lipid-soluble antioxidants through mechanisms seemingly unrelated to free-radical generation or scavenging.
authors.affiliation: Nestec Ltd, Nestlé Research Centre, Lausanne, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Guidoux
authors.forename: P
authors.initials: P
authors.lastname: Lambelet
authors.forename: J
authors.initials: J
authors.lastname: Phoenix
mesh_terms: D000090:Acetoacetates / Q000494:pharmacology; D000693:Anaerobiosis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002338:Carotenoids / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D000860:Hypoxia; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene
chemical_list: D000090:Acetoacetates; D000975:Antioxidants; D002839:Chromans; D009840:Oligomycins; D019207:beta Carotene; D014801:Vitamin A; D014451:Ubiquinone; D014810:Vitamin E; D002338:Carotenoids; C016635:acetoacetic acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D010100:Oxygen; D002118:Calcium