Jacobs 2013 Am J Physiol Endocrinol Metab

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Jacobs R, Meinild AK, Nordsborg NB, Lundby C (2013) Lactate oxidation in human skeletal muscle mitochondria. Am J Physiol Endocrinol Metab 304:686-94.

» PMID: 23384769 Open Access

Jacobs R, Meinild AK, Nordsborg NB, Lundby C (2013) Am J Physiol Endocrinol Metab

Abstract: Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we analyze the ability of skeletal muscle to respire lactate using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from the m. vastus lateralis in 16 human subjects. Samples were chemically permeabilized with saponin, which selectively perforates the sarcolemma and facilitates the loss of cytosolic content without altering mitochondrial membranes, structure, and subcellular interactions. High-resolution respirometry was performed on permeabilized muscle biopsy preparations. Using four separate and specific substrate titration protocols the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (p ≤ 0.003). The addition of exogenous LDH failed to increase lactate-stimulated respiration (p = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within the mitochondrial intermembrane space with the pyruvate subsequently taken into the mitochondrial matrix where it enters the TCA cycle and is ultimately oxidized. Keywords: Lactate metabolism, Mitochondrial function, Lactate oxidation complex

O2k-Network Lab: CH Zurich Lundby C, CH Zurich Gassmann M

Labels: MiParea: Respiration 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: TCA cycle and matrix dehydrogenases  Regulation: Substrate  Coupling state: LEAK, OXPHOS  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k