Title:Mitochondrial Carnitine/Acylcarnitine Translocase: Insights in Structure/ Function Relationships. Basis for Drug Therapy and Side Effects Prediction
Volume: 15
Issue: 5
Author(s): Annamaria Tonazzi, Nicola Giangregorio, Lara Console and Cesare Indiveri
Affiliation:
Keywords:
β-lactams, carnitine, mitochondria, mutagenesis, omeprazole, oxidative stress, red-ox regulation, transport activity.
Abstract: The mitochondrial carnitine/acylcarnitine translocase has been identified, purified and
reconstituted in liposomes in 1990. Since that time it has been object of studies aimed to characterize
its function and to define the molecular determinants of the translocation pathway. Thanks to these
tenacious studies the molecular map of the amino acids involved in the catalysis has been constructed
and the roles of critical residues in the translocation pathway have been elucidated. This has been
possible through the combination of transport assay in reconstituted liposomes, site-directed mutagenesis, chemical
labeling and bioinformatics. Recently some molecules which modulate CACT activity have been identified, such as
glutathione and hydrogen peroxide, constituting some of the few cases of control mechanisms of mitochondrial carriers.
The vast knowledge on the carnitine/acylcarnitine translocase is essential both as a progress in basic science and as
instrument to foresee therapeutic or toxic effects of xenobiotics and drugs. Such studies have been already started pointing
out the inhibitory action of drugs such as K+/H+-ATPase inhibitors (omeprazole) or antibiotics (β-lactams) on the
carnitine/acylcarnitine translocase, which can explain some of their adverse effects.