Drug-induced mitochondrial toxicity.
Mitochondria play a critical role in generating most of the cell's energy as ATP. They are also involved in other metabolic processes such as urea generation, haem synthesis and fatty acid beta-oxidation. Disruption of mitochondrial function by drugs can result in cell death by necrosis or can signal cell death by apoptosis (e.g., following cytochrome c release). Drugs that injure mitochondria usually do so by inhibiting respiratory complexes of the electron chain; inhibiting or uncoupling oxidative phosphorylation; inducing mitochondrial oxidative stress; or inhibiting DNA replication, transcription or translation. It is important to test for mitochondrial toxicity early in drug development as impairment of mitochondrial function can induce various pathological conditions that are life threatening or can increase the progression of existing mitochondrial diseases.
Chan
Katie
K
University of Toronto, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Toronto, Ontario, M5S 2S2, Canada.
Truong
Don
D
Shangari
Nandita
N
O'Brien
Peter J
PJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress; D014475:Uncoupling Agents / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007004:Hypoglycemic Agents; D024101:Mitochondrial Proteins; D014475:Uncoupling Agents