Abstract
Mitochondria have an important role in energy production, homeostasis and cell death. The opening of the mitochondrial permeability transition pore (mPTP) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin D (CyPD), a crucial component of this protein complex. In Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin A-dependent manner, a well-known cyclophilin inhibitor. In the present work, a mitochondrial parasite cyclophilin, named TcCyP22, which is homolog to the mammalian CyPD was identified. TcCyP22-overexpressing parasites showed an enhanced loss of mitochondrial membrane potential and loss of cell viability when exposed to a hydrogen peroxide stimulus compared with control parasites. Our results describe for the first time in a protozoan parasite that a mitochondrial cyclophilin is a component of the permeability transition pore and is involved in regulated cell death induced by oxidative stress.
Highlights
Mitochondria serve as the ‘powerhouse’ that provides near 90% of ATP necessary for cell life
Apoptosis was considered as the only form of regulated cell death but since late 1990s it has become clear that necrosis can occur in a regulated fashion, known as regulated necrosis (RN)
The mPT is capable of triggering a peculiar process of RN that critically relies on peptidyl prolyl isomerase F (PPIF, best known as cyclophilin D, CyPD), which results in the opening of a non-selective pore, namely the mitochondrial permeability transition pore
Summary
Mitochondria serve as the ‘powerhouse’ that provides near 90% of ATP necessary for cell life. Genotype have been shown to limit necrotic cell death, in vitro as well as in vivo, in a variety of pathophysiological settings including ischemia-reperfusion injuries of the heart,[7,8,9] brain[10,11] and kidneys.[12,13] Interestingly, the pro-necrotic activity of CyPD appears to be regulated by a mitochondrial pool of the oncosupressor protein p53.11 the precise molecular mechanisms that execute mPT-dependent RN is still obscure It remains to be formally demonstrated whether CyPD mediates RN as part of the mPTP or independently from the assembly of such a protein complex. As we intended to use the transgenic parasites in the epimastigote stage for further studies, we first attempted to evaluate if the overexpression of TcCyP22 altered parasite viability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
