title: Tl+ induces the permeability transition pore in Ca2+-loaded rat liver mitochondria energized by glutamate and malate.
abstract: It is known that Ca2+ and heavy metals more actively induce MPTP opening in mitochondria, energized by the I complex substrates. Thus, a rise in a Tl+-induced MPTP was proposed in experiments on isolated rat liver mitochondria energized by the complex I substrate (glutamate and malate). Expose of the mitochondria to Ca2+ into a medium containing TlNO3, glutamate, and malate as well as sucrose or KNO3 resulted in a decrease in state 3, state 4, or DNP-stimulated respiration as well as an increase of both mitochondrial swelling and ΔΨmito dissipation. The MPTP inhibitors, CsA and ADP, almost completely eliminated the effect of Ca2+, which was more pronounced in the presence of the complex I substrates than the complex II substrate (succinate) and rotenone (Korotkov and Saris, 2011). The present study concludes that Tl+-induced MPTP opening is more appreciable in mitochondria energized by glutamate and malate but not succinate in the presence of rotenone. We assume that the Tl+-induced MPTP opening along with followed swelling and possible structural deformations of the complex I in Ca2+-loaded mitochondria may be a part of the thallium toxicity mechanism on mitochondria in living organisms. At the same time, oxidation of Tl+ to Tl3+ by mitochondrial oxygen reactive species is proposed for the mechanism.
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223 St., Petersburg, Russian Federation. 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, Russian Federation.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Emelyanova
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223 St., Petersburg, Russian Federation.
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, Russian Federation.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Brailovskaya
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D008293:Malates / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D009566:Nitrates / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D017680:Potassium Compounds / Q000494:pharmacology; D017208:Rats, Wistar; D013395:Sucrose / Q000494:pharmacology; D013793:Thallium / Q000633:toxicity*
chemical_list: D008293:Malates; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009566:Nitrates; D017680:Potassium Compounds; D018698:Glutamic Acid; D013395:Sucrose; C030298:malic acid; D013793:Thallium; C023844:potassium nitrate; D002118:Calcium
keywords: Mitochondrial complex I; Mitochondrial permeability transition; Mitochondrial respiration; Mitochondrial swelling; Rat liver mitochondria; Tl(+)