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The Thiazolidinedione Pioglitazone Alters Mitochondrial Function in Human Neuron-Like Cells

Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia

Thiazolidinediones alter cell energy metabolism. They are used to treat or are being considered for the treatment of disorders that feature mitochondrial impairment. Their mitochondrial effects, however, have not been comprehensively studied under long-term exposure conditions. We used the human neuron-like NT2 cell line to directly assess the long-term effects of a thiazolidinedione drug, pioglitazone, on mitochondria. At micromolar concentrations, pioglitazone increased mitochondrial DNA (mtDNA) content, levels of mtDNA and nuclear-encoded electron transport chain subunit proteins, increased oxygen consumption, and elevated complex I and complex IV V_max activities. Pioglitazone treatment was also associated with increased cytoplasmic but reduced mitochondrial peroxide levels. Our data suggest that pioglitazone induces mitochondrial biogenesis and show that pioglitazone reduces mitochondrial oxidative stress in a neuron-like cell line. For these reasons pioglitazone may prove useful in the treatment of mitochondriopathies.

Received for publication December 29, 2006.

Accepted for publication March 26, 2007.

Address correspondence to: Dr. Russell H. Swerdlow, #800394, Department of Neurology, McKim Hall, 1 Hospital Drive, Charlottesville, VA 22908. E-mail: rhs7e{at}virginia.edu

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