Drug-induced mitochondrial toxicity.
Drug-induced mitochondrial toxicity.
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DOI：
10.1517/17425255.1.4.655
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发表时间：
2005-12-01
影响因子：
4.3
通讯作者：
O'Brien, Peter J
中科院分区：
文献类型：
--
作者：
Chan, Katie;Truong, Don;O'Brien, Peter J
线粒体在产生细胞的大部分能量（如ATP）方面起着关键作用。它们还参与其他代谢过程，如尿素生成、血红素合成和脂肪酸β-氧化。药物对线粒体功能的破坏可导致通过坏死的细胞死亡或可通过凋亡发出细胞死亡的信号（例如，细胞色素C释放后）。损伤线粒体的药物通常通过抑制电子链的呼吸复合物;抑制或解偶联氧化磷酸化;诱导线粒体氧化应激;或抑制DNA复制、转录或翻译来实现。在药物开发早期检测线粒体毒性非常重要，因为线粒体功能受损可诱导各种危及生命的病理状况或可加速现有线粒体疾病的进展。
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.