Plasmodium spp. membrane glutathione S-transferases: detoxification units and drug targets
Authors:Andreas Martin Lisewski
Department of Molecular and Human Genetics, Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Keywords:
Plasmodium, malaria, detoxification, glutathione, artemisinin.
Related Article(s)?
Lisewski AM, Quiros JP, Ng CL, Adikesavan AK, Miura K, Putluri N, Eastman RT, Scanfeld D, Regenbogen SJ, Altenhofen L, Llinás M, Sreekumar A, Long C, Fidock DA and Lichtarge O (2014). Supergenomic network compression and the discovery of EXP1 as a glutathione transferase Inhibited by artesunate. Cell 158(4):916-28. , 10.1016/j.cell.2014.07.011
Corresponding Author(s):
Conflict of interest statement:
The author declares no conflicts of interest.
Please cite this article as:
Andreas Martin Lisewski (2014). Plasmodium spp. membrane glutathione S-transferases: detoxification units and drug targets. Microbial Cell 1(11): 387-389.
© 2014 Lisewski. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Membrane glutathione S-transferases from the class of membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) form a superfamily of detoxification enzymes that catalyze the conjugation of reduced glutathione (GSH) to a broad spectrum of xenobiotics and hydrophobic electrophiles. Evolutionarily unrelated to the cytosolic glutathione S-transferases, they are found across bacterial and eukaryotic domains, for example in mammals, plants, fungi and bacteria in which significant levels of glutathione are maintained. Species of genus Plasmodium, the unicellular protozoa that are commonly known as malaria parasites, do actively support glutathione homeostasis and maintain its metabolism throughout their complex parasitic life cycle. In humans and in other mammals, the asexual intraerythrocytic stage of malaria, when the parasite feeds on hemoglobin, grows and eventually asexually replicates inside infected red blood cells (RBCs), is directly associated with host disease symptoms and during this critical stage GSH protects the host RBC and the parasite against oxidative stress from parasite-induced hemoglobin catabolism. In line with these observations, several GSH-dependent Plasmodium enzymes have been characterized including glutathione reductases, thioredoxins, glyoxalases, glutaredoxins and glutathione S-transferases (GSTs); furthermore, GSH itself have been found to associate spontaneously and to degrade free heme and its hydroxide, hematin, which are the main cytotoxic byproducts of hemoglobin catabolism. However, despite the apparent importance of glutathione metabolism for the parasite, no membrane associated glutathione S-transferases of genus Plasmodium have been previously described. We recently reported the first examples of MAPEG members among Plasmodium spp.
doi: 10.15698/mic2014.11.177
Volume 1, pp. 387 to 389, published 23/10/2014.