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First published online on April 26, 2002.
 Copyright © 2002 by The Physiological Society
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2002.016683v1
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Received January 9, 2002
Accepted after revision April 18, 2002

No evidence of an intracellular lactate shuttle in skeletal muscle

K. Sahlin1*, Maria Fernström2, Michael Svensson2, and Michail Tonkonogi2

1 Department of Physiology and Pharmacology, Karolinska Institutet, Box 5626, SE 114 86, Stockholm, Sweden
2 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm and Department of Sport and Health Sciences, Stockholm University College of Physical Education and Sports, Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: kent.sahlin{at}fyfa.ki.se.

The concerted view is that cytosolic pyruvate is transferred into mitochondria and after oxidative decarboxylation further metabolized in the tricarboxylic acid cycle. In a recent paper, Brooks et al. (1999) challenge this view and conclude that mitochondria predominantly oxidize lactate in vivo and that an 'intracellular lactate shuttle' exists in muscle. This view appears to be gaining acceptance in the scientific community and due to its conceptual importance, confirmation by independent experiments is required. We have repeated the experiments in mitochondria isolated from rat soleus muscle. Contrary to the findings presented by Brooks et al. (1999), we cannot find any mitochondrial respiration with lactate. Even when external lactate dehydrogenase (LDH) was added to mitochondria, there were no signs of respiration with lactate. However, in the presence of conditions where lactate is converted to pyruvate (external additions of both LDH and NAD+), mitochondrial oxygen consumption increased. Analysis of LDH by spectrophotometry demonstrated that the activity in the mitochondrial fraction was only 0.7 % of total activity. Furthermore, we provide theoretical evidence that direct mitochondrial lactate oxidation is energetically unlikely. Based on the present data we conclude that direct mitochondrial lactate oxidation does not occur in skeletal muscle. The presence of an 'intracellular lactate shuttle' can therefore be questioned.




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