ReviewDrug induced mitochondrial dysfunction: Mechanisms and adverse clinical consequences

- Drug induced mitochondrial dysfunction is associated with many adverse drug reactions.
- Drugs can affect mitochondria directly by inhibiting ETC, mtDNA transcription, protein production and ATP synthesis.
- Increased ROS production can contribute to mitochondrial dysfunction indirectly by damaging mtDNA and the OXPHOS system.
- Knowledge of adverse drug-mitochondrial interactions may help clinicians design safer drug therapies for patients.

Several commonly used medications impair mitochondrial function resulting in adverse effects or toxicities. Drug induced mitochondrial dysfunction may be a consequence of increased production of reactive oxygen species, altered mitochondrial permeability transition, impaired mitochondrial respiration, mitochondrial DNA damage or inhibition of beta-oxidation of fatty acids. The clinical manifestation depends on the specific drug and its effect on mitochondria. Given the ubiquitous presence of mitochondria and its central role in cellular metabolism, drug-mitochondrial interactions may manifest clinically as hepatotoxicity, enteropathy, myelosuppression, lipodystrophy syndrome or neuropsychiatric adverse effects, to name a few. The current review focuses on specific drug groups which adversely affect mitochondria, the mechanisms involved and the clinical consequences based on the data available from experimental and clinical studies. Knowledge of these adverse drug-mitochondrial interactions may help the clinicians foresee potential issues in individual patients, prevent adverse drug reactions or alter drug regimens to enhance patient safety.