Two separate pathways for d-lactate oxidation by Saccharomyces cerevisiae mitochondria which differ in energy production and carrier involvement

AbstractIn this work we looked at whether and how mitochondria isolated from Saccharomyces cerevisiae (SCM) oxidize d-lactate. We found that:(1)externally added d-lactate causes oxygen uptake by SCM with P/O ratio equal to 1.5; in the presence of antimycin A (AA), P/O ratio was 1.8, differently in the presence of the non-penetrant α-cyanocinnamate (α-CCN−) no P/O ratio could be measured. Consistently, mitochondrial electrical membrane potential (Δψ) generation was found, due to externally added d-lactate in the presence of antimycin A, but not of α-CCN−.(2)SCM oxidize d-lactate in two different manners: (i) via inner membrane d-lactate dehydrogenase which leads to d-lactate oxidation without driving Δψ generation and ATP synthesis and (ii) via the matrix d-lactate dehydrogenase, which drives Δψ generation and ATP synthesis by using taken up d-lactate.(3)Pyruvate newly synthesised in the mitochondrial matrix is exported via the novel d-lactate/pyruvate antiporter. d-Lactate/pyruvate antiport proved to regulate the rate of pyruvate efflux in vitro.(4)The existence of the d-lactate/H+ symporter is also proposed as shown by mitochondrial swelling.The d-lactate carriers and d-lactate dehydrogenases could account for the removal of the toxic methylglyoxal from cytosol, as well as for the d-lactate-dependent gluconeogenesis