TY - JOUR T1 - The Thiazolidinedione Pioglitazone Alters Mitochondrial Function in Human Neuron-Like Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1695 LP - 1702 DO - 10.1124/mol.106.033845 VL - 71 IS - 6 AU - Sangeeta Ghosh AU - Nishant Patel AU - Douglas Rahn AU - Jenna McAllister AU - Sina Sadeghi AU - Geoffrey Horwitz AU - Diana Berry AU - Kai Xuan Wang AU - Russell H. Swerdlow Y1 - 2007/06/01 UR - http://molpharm.aspetjournals.org/content/71/6/1695.abstract N2 - 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 Vmax 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. The American Society for Pharmacology and Experimental Therapeutics ER -