In the present study we investigated whether isolated rat liver mitochondria can take up and metabolize d-lactate. We found the following: (1) externally added d-lactate causes oxygen uptake by mitochondria [P/O ratio (the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation) = 2] and membrane potential (Δψ) generation in processes that are rotenone-insensitive, but inhibited by antimycin A and cyanide, and proton release from coupled mitochondria inhibited by α-cyanocinnamate, but not by phenylsuccinate; (2) the activity of the putative flavoprotein (d-lactate dehydrogenase) was detected in inside-out submitochondrial particles, but not in mitochondria and mitoplasts, as it is localized in the matrix phase of the mitochondrial inner membrane; (3) three novel separate translocators exist to mediate d-lactate traffic across the mitochondrial inner membrane: the d-lactate/H+ symporter, which was investigated by measuring fluorimetrically the rate of endogenous flavin reduction, the d-lactate/oxoacid antiporter (which mediates both the d-lactate/pyruvate and d-lactate/oxaloacetate exchanges) and d-lactate/malate antiporter studied by monitoring photometrically the appearance of the d-lactate counteranions outside mitochondria. The d-lactate translocators, in the light of their different inhibition profiles separate from the monocarboxylate carrier, were found to differ from each other in the Vmax values and in the inhibition and pH profiles and were shown to regulate mitochondrial d-lactate metabolism in vitro. The d-lactate translocators and the d-lactate dehydrogenase could account for the removal of the toxic methylglyoxal from cytosol, as well as for d-lactate-dependent gluconeogenesis.
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July 2002
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Research Article|
July 15 2002
d-Lactate transport and metabolism in rat liver mitochondria
Lidia de BARI;
Lidia de BARI
∗Dipartimento di Biochimica e Biologia Molecolare, Università di Bari, Via Orabona 4, 70126 Bari, Italy
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Anna ATLANTE;
Anna ATLANTE
†Centro di Studio sui Mitocondri e Metabolismo Energetico, CNR, Via G. Amendola, 165A, 70126 Bari, Italy
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Nicoletta GUARAGNELLA;
Nicoletta GUARAGNELLA
∗Dipartimento di Biochimica e Biologia Molecolare, Università di Bari, Via Orabona 4, 70126 Bari, Italy
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Giovanni PRINCIPATO;
Giovanni PRINCIPATO
‡Istituto di Biologia e Genetica, Facoltà di Medicina e Chirurgia, Università di Ancona, Via Ranieri, Montedago, 60100 Ancona, Italy
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Salvatore PASSARELLA
Salvatore PASSARELLA
1
§Dipartimento di Scienze Animali, Vegetali e dell'Ambiente, Università del Molise, Via De Sanctis, 86100 Campobasso, Italy
1To whom correspondence should be addressed (e-mail passarel@unimol.it).
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Publisher: Portland Press Ltd
Received:
January 23 2002
Revision Received:
April 03 2002
Accepted:
April 09 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 365 (2): 391–403.
Article history
Received:
January 23 2002
Revision Received:
April 03 2002
Accepted:
April 09 2002
Citation
Lidia de BARI, Anna ATLANTE, Nicoletta GUARAGNELLA, Giovanni PRINCIPATO, Salvatore PASSARELLA; d-Lactate transport and metabolism in rat liver mitochondria. Biochem J 15 July 2002; 365 (2): 391–403. doi: https://doi.org/10.1042/bj20020139
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