Prescription drugs and mitochondrial metabolism

• Published in: Bioscience reports Vol. 42; no. 4; p. 1
• Main Author: Schmidt, Cameron A
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 01.04.2022; Portland Press Ltd
• Subjects: Adenosine diphosphate; Antibiotics; Antidepressants; Bioenergetics; Calcium ions; Calcium sequestration; Complexity; Drug interaction; Drug interactions; Drug metabolism; Energy; Energy Metabolism; Energy transduction; Heart; High-throughput screening; Liver; Metabolism; Metabolites; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mutation; Natural products; Ontology; Oxidative Phosphorylation; Pharmacokinetics; Pharmacology & Toxicology; Phosphorylation; Physiological effects; Physiology; Prescription drugs; Prescription Drugs - metabolism; Prescription Drugs - pharmacology; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Respiration; Review; Side effects; Therapeutics & Molecular Medicine; Pharmacology; Prescription Drugs; Metabolism; Xenobiotics; mitochondria
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20211813

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.