title: Drug-Induced Mitochondrial Toxicity.
abstract: The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy.
authors.affiliation: Neurometabolic Unit. Box 105, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK. i.hargreaves@ucl.ac.uk.|Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK. i.hargreaves@ucl.ac.uk.
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.affiliation: Neurometabolic Unit. Box 105, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Department of Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK.|College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
authors.forename: Mesfer
authors.initials: M
authors.lastname: Al Shahrani
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Wainwright
authors.affiliation: Neurometabolic Unit. Box 105, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK.|Department of Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK.|Laboratory Medicine, Great Ormond Street Hospital, London, UK.
authors.forename: Simon J R
authors.initials: SJ
authors.lastname: Heales
mesh_terms: D019440:Anti-Obesity Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D000928:Antidepressive Agents / Q000009:adverse effects; D000975:Antioxidants / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D000975:Antioxidants; D007980:Levodopa