Prescription drugs and mitochondrial metabolism.
Prescription drugs and mitochondrial metabolism.
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DOI：
10.1042/bsr20211813
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发表时间：
2022-04-29
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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作者：
线粒体是几乎所有真核细胞的生理和存活的核心，并且容纳多种代谢过程，包括氧化磷酸化、活性氧缓冲、代谢物合成/交换和Ca 2+螯合。线粒体在表型上是异质的，这种变异对于细胞、组织和器官系统之间生理功能的复杂性是必不可少的。作为线粒体与如此多的生理过程整合的结果，调节线粒体代谢的小分子诱导复杂的全身效应。在许多常用处方药的情况下，这些相互作用可能有助于药物治疗机制，诱导药物不良反应，或两者兼而有之。本文的目的是回顾历史和最近的进展，了解处方药对线粒体代谢的影响。特定的“模式”的外源性线粒体相互作用进行了讨论，以提供一组定性的模型，有助于概念化的线粒体能量转导系统可能会受到影响。最近在体外高通量筛选研究的结果进行了审查，并选择了一些候选药物类别进行额外的简要讨论（即抗高血糖，抗抑郁药，抗生素，抗高血压）。最后，最近的改进，有助于量化药物-线粒体相互作用的全身效应的药代动力学模型进行了简要的考虑。
Mitochondria are central to the physiology and survival of nearly all eukaryotic cells and house diverse metabolic processes including oxidative phosphorylation, reactive oxygen species buffering, metabolite synthesis/exchange, and Ca2+ sequestration. Mitochondria are phenotypically heterogeneous and this variation is essential to the complexity of physiological function among cells, tissues, and organ systems. As a consequence of mitochondrial integration with so many physiological processes, small molecules that modulate mitochondrial metabolism induce complex systemic effects. In the case of many commonly prescribed drugs, these interactions may contribute to drug therapeutic mechanisms, induce adverse drug reactions, or both. The purpose of this article is to review historical and recent advances in the understanding of the effects of prescription drugs on mitochondrial metabolism. Specific ‘modes’ of xenobiotic–mitochondria interactions are discussed to provide a set of qualitative models that aid in conceptualizing how the mitochondrial energy transduction system may be affected. Findings of recent in vitro high-throughput screening studies are reviewed, and a few candidate drug classes are chosen for additional brief discussion (i.e. antihyperglycemics, antidepressants, antibiotics, and antihyperlipidemics). Finally, recent improvements in pharmacokinetics models that aid in quantifying systemic effects of drug–mitochondria interactions are briefly considered.
DOI：
10.1002/psp4.12230
发表时间：
2017-11
期刊：
CPT: pharmacometrics & systems pharmacology
影响因子：
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作者：
Maldonado EM;Leoncikas V;Fisher CP;Moore JB;Plant NJ;Kierzek AM
通讯作者：
Kierzek AM