Assessment of the Effects of Drugs on Mitochondrial Respiration

Methods Mol Biol. 2021:2277:133-142. doi: 10.1007/978-1-0716-1270-5_9.

Abstract

Mitochondria are targets of newly synthesized drugs and being tested for the treatment of various diseases caused or accompanied by disruption of cellular bioenergetics. In drug development, it is necessary to test for drug-induced changes in mitochondrial enzyme activity that may be related to therapeutic or adverse drug effects. Measurement of drug effect on mitochondrial oxygen consumption kinetics and/or protective effects of drugs against calcium-induced inhibition of the mitochondrial respiration can be used for the study mitochondrial toxicity and neuroprotective effects of drugs. Supposing that the drug-induced inhibition of the mitochondrial respiratory rate and/or individual mitochondrial complexes is associated with adverse drug effects, the effects of drugs on mitochondrial respiration in isolated mitochondria allow selection of novel molecules that are relatively safe for mitochondrial toxicity.

Keywords: Drug development; High-resolution respirometry; Isolated mitochondria; Mitochondrial respiration; Mitochondrial toxicity; Pig brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Drug Evaluation, Preclinical / instrumentation
  • Drug Evaluation, Preclinical / methods*
  • Electron Transport Complex I / metabolism
  • Electron Transport Complex III / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Swine

Substances

  • Electron Transport Complex I
  • Electron Transport Complex III