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Mitochondrial activation and the pyruvate paradox in a human cell line
Author(s) -
de Andrade Paula B.M.,
Casimir Marina,
Maechler Pierre
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.088
Subject(s) - hyperpolarization (physics) , depolarization , mitochondrion , cytosol , membrane potential , pyruvate dehydrogenase complex , pyruvate decarboxylation , biophysics , nad+ kinase , inner mitochondrial membrane , pyruvate dehydrogenase kinase , citric acid cycle , chemistry , biochemistry , microbiology and biotechnology , biology , metabolism , stereochemistry , enzyme , nuclear magnetic resonance spectroscopy
Pyruvate promotes hyperpolarization of the inner mitochondrial membrane. However, in isolated mitochondria, pyruvate could participate in a futile cycle leading to mitochondrial depolarization. Here, we investigated this paradox in intact human cells by measuring parameters reflecting mitochondrial activation in response to 1 mM pyruvate and 5 mM glucose. NAD(P)H levels were elevated similarly by both substrates. Conversely, pyruvate induced a first transient phase of mitochondrial depolarization before the establishment of the expected sustained hyperpolarization. This correlated with kinetics of cytosolic ATP levels exhibiting a first phase decrease followed by an increase. Therefore, pyruvate transiently depolarizes mitochondria and reduces ATP in intact cells.