Current Concepts in Drug‐Induced Mitochondrial Toxicity

Sashi Nadanaciva1, Yvonne Will1

1 Pfizer Inc., Groton, Connecticut
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 2.15
DOI:  10.1002/0471140856.tx0215s40
Online Posting Date:  May, 2009
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Abstract

Mitochondria generate most of the cell's ATP and play key roles in fatty acid oxidation, steroid synthesis, heme synthesis, thermogenesis, calcium homeostasis, and apoptosis. With the development of new methods to study mitochondrial function, it is becoming clear that drug‐induced mitochondrial dysfunction is one of the causes of drug toxicity. Mitochondria can be impaired by drugs in a variety of ways. These include inhibition of oxidative phosphorylation, uncoupling of electron transport from ATP synthesis, irreversible opening of the mitochondrial permeability transition pore, inhibition of transporters within the mitochondrial inner membrane, increased oxidative stress, inhibition of the citric acid cycle, inhibition of fatty acid oxidation, and impairment of either mtDNA replication or mtDNA‐encoded protein synthesis. This unit provides an overview on the physiological roles of mitochondria and the mechanisms by which they can be adversely affected by drugs. Curr. Protoc. Toxicol. 40:2.15.1‐2.15.9. © 2009 by John Wiley & Sons, Inc.

Keywords: toxicity; mitochondria; energy production; ROS; apoptosis; mtDNA; mt ribosomes; drug toxicity

     
 
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Table of Contents

  • Introduction
  • Energy Production in Mitochondria
  • Mitochondria and Reactive Oxygen Species
  • Mitochondria and Apoptosis
  • Mitochondrial DNA and Mitochondrial Ribosomes
  • Drug‐Induced Mitochondrial Toxicity
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

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Literature Cited

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