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Lactate oxidation in human skeletal muscle mitochondria
Robert A Jacobs1, Anne-Kristine Meinild, Nikolai B Nordsborg
1Zurich Center for Integrative Human Physiology, Zurich, Switzerland. jacobs@vetphys.uzh.ch
American Journal of Physiology. Endocrinology and Metabolism
|February 7, 2013
Summary
Human skeletal muscle mitochondria can oxidize lactate, but not directly. Lactate is converted to pyruvate in the intermembrane space before entering the TCA cycle for oxidation.
Area of Science:
- Human physiology
- Cellular metabolism
- Mitochondrial function
Background:
- Lactate is a key energy metabolite oxidized in various human tissues.
- The precise mechanisms of lactate metabolism in tissues like skeletal muscle remain incompletely understood.
Purpose of the Study:
- To investigate the capacity of human skeletal muscle mitochondria to respire lactate.
- To elucidate the specific site and mechanism of lactate oxidation within skeletal muscle cells.
Main Methods:
- Utilized high-resolution respirometry on chemically permeabilized vastus lateralis muscle biopsies from 16 human subjects.
- Employed specific substrate titration protocols to assess mitochondrial respiration with lactate and NAD(+).
- Investigated the role of lactate dehydrogenase (LDH) in lactate oxidation.
Main Results:
- Permeabilized skeletal muscle mitochondria demonstrated the ability to oxidize lactate independently of exogenous LDH.
- Titration of lactate and NAD(+) significantly stimulated mitochondrial respiration (P ≤ 0.003).
- Exogenous LDH did not enhance lactate-stimulated respiration (P = 1.0), indicating LDH is not rate-limiting.
Conclusions:
- Human skeletal muscle mitochondria do not directly oxidize lactate within the mitochondrial matrix.
- Lactate is likely converted to pyruvate in the mitochondrial intermembrane space.
- Pyruvate then enters the mitochondrial matrix to fuel the TCA cycle for oxidation.
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