The thiazolidinedione pioglitazone alters mitochondrial function in human neuron-like cells.
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.
Ghosh
Sangeeta
S
Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Patel
Nishant
N
Rahn
Douglas
D
McAllister
Jenna
J
Sadeghi
Sina
S
Horwitz
Geoffrey
G
Berry
Diana
D
Wang
Kai Xuan
KX
Swerdlow
Russell H
RH
D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D004272:DNA, Mitochondrial; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000077205:Pioglitazone; D017382:Reactive Oxygen Species / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D000077205:Pioglitazone