TY - JOUR
T1 - Mitochondrial off targets of drug therapy
AU - Wallace, Kendall B.
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.tips.2008.04.001
DO - 10.1016/j.tips.2008.04.001
M3 - Review article
C2 - 18501972
AN - SCOPUS:45849132031
SN - 0165-6147
VL - 29
SP - 361
EP - 366
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 7
ER -