Mitochondrial off targets of drug therapy

Research output: Contribution to journalReview articlepeer-review

72 Scopus citations

Abstract

The bioenergetic features of mitochondria have long been exploited in the design of pharmacological agents suited to accomplish a desired physiological effect; uncoupling of oxidative phosphorylation to induce weight loss, for example. However, more recent experience demonstrates mitochondria to be unintended off targets of other drug therapies and responsible, at least in part, for the dose-limiting adverse events associated with a large array of pharmaceuticals. Review of the fundamentals of mitochondrial molecular biology and bioenergetics reveals a multiplicity of off targets that can be invoked to explain drug-induced mitochondrial failure. It is this redundancy of mitochondrial off targets that complicates identification of discrete mechanisms of toxicity and confounds QSAR-based design of new small molecules devoid of this potential for mitochondrial toxicity. The present review article briefly reviews the molecular biology and biophysics of mitochondrial bioenergetics, which then serves as a platform for identifying the various potential off targets for drug-induced mitochondrial toxicity.

Original languageEnglish (US)
Pages (from-to)361-366
Number of pages6
JournalTrends in Pharmacological Sciences
Volume29
Issue number7
DOIs
StatePublished - Jul 2008

Bibliographical note

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

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