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Review
. 2022 Mar 18;23(6):3315.
doi: 10.3390/ijms23063315.

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

Milos Mihajlovic  1 , Mathieu Vinken  1
Affiliations
Review

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

Milos Mihajlovic et al. Int J Mol Sci. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the main mitochondrial functions in a cell. Created with Biorender.com (accessed on 21 February 2022; Toronto, ON, Canada) (ATP—adenosine triphosphate).
Figure 2
Figure 2
Schematic representation of the main hepatic metabolic functions in which mitochondria have a critical role. Created with Biorender.com (accessed on 21 February 2022; Toronto, ON, Canada).
Figure 3
Figure 3
Schematic representation of the main mechanisms and consequences of drug-induced mitochondrial dysfunction. Created with Biorender.com (accessed on 21 February 2022; Toronto, ON, Canada). (MPTP—mitochondrial permeability transition pore; OXPHOS—oxidative phosphorylation; ATP—adenosine triphosphate; ROS—reactive oxygen species; mtDNA—mitochondrial DNA).
Figure 4
Figure 4
Schematic representation of the main factors affecting susceptibility to hepatic injury due to drug-induced mitochondrial toxicity. Created with Biorender.com (accessed on 21 February 2022; Toronto, ON, Canada).
See this image and copyright information in PMC

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