title: Diamide accelerates opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.
abstract: Opening of the mitochondrial permeability transition pore (MPTP) in the inner membrane is due to matrix Ca(2+) overload and matrix glutathione loss. Fixing the 'm' conformation of the adenine nucleotide translocase (ANT) by ADP or N-ethylmaleimide (NEM) inhibits opening of the MPTP. Oxidants (diamide or tert-butylhydroperoxide (tBHP)) fix the ANT in 'c' conformation, and the ability of ADP to inhibit the MPTP is thus attenuated. Earlier we found (Korotkov and Saris, 2011) that calcium load of rat liver mitochondria resulted in Tl(+)-induced MPTP opening, which was accompanied by a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration, as well as increased swelling and membrane potential dissipation. These effects, which were increased by diamide and tBHP, were visibly reduced in the presence of the MPTP inhibitors (ADP, NEM, and cyclosporine A). Our data suggest that conformational changes of the ANT and matrix glutathione loss may be directly involved in opening the Tl(+)-induced MPTP in the inner membrane of Ca(2+)-loaded rat liver mitochondria.
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russia. Electronic address: korotkov@SK1645.spb.edu.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Korotkov
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russia.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Konovalova
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Brailovskaya
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016877:Oxidants; D003958:Diamide; D000244:Adenosine Diphosphate; D000226:Mitochondrial ADP, ATP Translocases; D020122:tert-Butylhydroperoxide; D005033:Ethylmaleimide; D002118:Calcium
keywords: Adenine nucleotide translocase; Diamide; Glutathione oxidation; Mitochondrial permeability transition; Rat liver mitochondria; Tl(+)