Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Int J Mol Sci. 2022 Mar 18;23(6):3315. doi: 10.3390/ijms23063315.

Abstract

One of the major mechanisms of drug-induced liver injury includes mitochondrial perturbation and dysfunction. This is not a surprise, given that mitochondria are essential organelles in most cells, which are responsible for energy homeostasis and the regulation of cellular metabolism. Drug-induced mitochondrial dysfunction can be influenced by various factors and conditions, such as genetic predisposition, the presence of metabolic disorders and obesity, viral infections, as well as drugs. Despite the fact that many methods have been developed for studying mitochondrial function, there is still a need for advanced and integrative models and approaches more closely resembling liver physiology, which would take into account predisposing factors. This could reduce the costs of drug development by the early prediction of potential mitochondrial toxicity during pre-clinical tests and, especially, prevent serious complications observed in clinical settings.

Keywords: hepatotoxicity; in vitro; liver injury; mitochondrial dysfunction; molecular mechanisms.

Publication types

  • Review

MeSH terms

  • Chemical and Drug Induced Liver Injury* / diagnosis
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Drug-Related Side Effects and Adverse Reactions* / metabolism
  • Humans
  • Liver / metabolism
  • Mitochondria / metabolism
  • Mitochondria, Liver / metabolism