The existence in Saccharomyces cerevisiae of a protective mechanism in response to methylglyoxal: the role of D-lactate movement across the inner mitochondrial membrane and its function on gluconeogenesis.
Maria Luigia Pallotta
S.A.V.A, University of Molise, Via De Sanctis, Campobasso, 86100, Italy
Methylglyoxal (MG), an intrinsic intermediate of glycolysis, is an extremely toxic compound, able to react with, and modify, different molecular targets. In yeast a established pathway for MG detoxification by the action of the glyoxalase system converts, in the cytosol, MG into D-Lactate in the presence of glutathione [Aguilera et al, 2004]. Previous studies have already reported that isolated Saccharomyces cerevisiae mitochondria can take up and oxidise D-lactate externally added to them and shown the existence of two carriers for D-lactate mitochondrial metabolism: D-lactate/H+ symporter and D-lactate/pyruvate antiporter (Pallotta et al, 2004). Moreover, the role of the two mitochondrial enzymes (Dld1p and Dld2p) that accomplish D-lactate oxidation was studied. Here, a novel aspect the occurrence of a D-lactate/L-malate antiporter activity is highlighted. This activity differs from that of the D-lactate/pyruvate carrier in a)kinetics (Km and Vmax values are about 20 microM and 5.8 nmol min(-1) mg protein(-1) and 27 microM and 140 nmol min(-1) mg protein(-1), respectively), b)sensitivity to inhibitors, and c) pH profiles. D-lactate translocators, Dld1p and Dld2p could account for the removal of the toxic methylglyoxal as well as to supply pyruvate and malate, in the cytosol, for gluconeogenesis. References: Anguilera J., Prieto J.A.(2004) FEMS Yeast Research 4, 633-641. Pallotta M.L., Valenti D., Iacovino M., Passerella S. (2004) Biochimica et Biophysica Acta 1608, 104-113.
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