Mitochondrial permeability transition in protozoan parasites: what we learned from Trypanosoma cruzi

Abstract

Regulated cell death (RCD) involves a genetically encoded molecular machinery, which can be altered by means of pharmacologic and/or genetics interventions targeting the key components of such machinery. A variant of RCD that often manifests with necrotic morphotype critically relies on Cyclophilin D (CyPD), a mitochondrial matrix peptidyl-prolyl isomerase, which is encoded by the Ppif gene. A lot a research has been done in mammals, but still very little is known for protozoan parasites, one of the most ancient phylogenic branches of unicellular eukaryotes. In the present work, we revised the knowledge about mitochondrial permeability transition and regulated cell death in the parasite Trypanosoma cruzi, the causative agent of Chagas disease, that affects 7?8 million people only in South America as well as in other parts of the world through migrations from endemic areas. We also included other protozoan parasites of medical importance to briefly summarize and compare what is known so far about this exciting field of parasitology. We finalized the present article explaining the finding that a homologue of Cyclophilin D, which is the unique genetically confirmed regulator of the mitochondrial permeability transition in mammalian cells, is also expressed in T. cruzi and may be involved in regulated cell death in the parasite. These results were published earlier this year in Cell Death Discovery (Cell Death Discov 3, 16092. 2017 Feb 06). To our knowledge, this is the only Cyclophilin D homologue that has been described in a protozoan parasite. We consider that this parasite mitochondrial cyclophilin could be a valuable drug target for the therapeutic of Chagas disease.