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Tag: Roberto Docampo

Membrane contact activation of Piezo2 drives lysosome-mitochondrion Ca2+ transfer and signaling in Trypanosoma cruzi

  Calcium ion (Ca2+) transfer from other organelles is central to mitochondrial metabolism and cell survival, yet how mechanical forces regulate interorganelle communication remains unclear. Here we report a lysosome-to-mitochondrion pathway in Trypanosoma cruzi, the etiologic agent of Chagas disease, mediated by the mechano/osmosensitive channel TcPiezo2. Using ultrastructural, biochemical, and live-cell superresolution imaging, we define …

BDF6 Deficiency Severely Compromises Intracellular Amastigote Development and Infectivity of Trypanosoma cruzi

Trypanosoma cruzi, the causative agent of Chagas disease, relies on complex gene regulatory mechanisms to adapt to its diverse host environments. In recent years, it has been established that epigenetics plays an essential role in these mechanisms via the regulation of chromatin structure. Bromodomain-containing factors (BDFs), known for recognizing acetylated lysines on histones, have emerged …

Selenocyanate-Containing Molecules as Trypanosoma cruzi Inhibitors: Impact of Regioisomerism, Conformational Restriction, and Second-Ring Substitution

As a continuation of the project aimed at searching for new chemotherapeuticagents against Chagas disease or American trypanosomiasis, new selenocyanate derivatives are designed, synthesized, and biologically evaluated against the clinically more relevant dividing amastigote form of Trypanosoma cruzi, the etiologic agent of this illness. Furthermore, as all the title compounds are fluorine-containing molecules, it seemed …

Chemical and Genetic Validation of an Essential Calcium Entry Channel of Trypanosoma brucei as a Therapeutic Target

The Trypanosoma brucei group of parasites causes Nagana in cattle and human African trypanosomiasis, or sleeping sickness, in humans. Current drugs against these parasites have severe toxicity, vaccines are not available, and development of drug resistance makes finding new chemotherapeutic targets imperative. Ion channels, which are involved in several biological processes, are targets of many therapeutically useful …

Lysosome and plasma membrane Piezo channels of Trypanosoma cruzi are essential for proliferation, differentiation and infectivity

Trypanosoma cruzi, the causative agent of Chagas disease, is a parasitic protist that affects millions of people worldwide. Currently there are no fully effective drugs or vaccines available. Contact of T. cruzi infective forms with their host cells or with the extracellular matrix increases their intracellular Ca2+ concentration suggesting a mechano-transduction process. We report here …

Acidocalcisome localization of membrane transporters and enzymes in Trypanosoma brucei

  Acidocalcisomes of Trypanosoma brucei are membrane-bounded organelles characterized by their acidity and high content of polyphosphate and cations, like calcium and magnesium. They have important roles in cation and phosphorus storage, osmoregulation, autophagy initiation, calcium signaling, and virulence. Acidocalcisomes of T. brucei possess several membrane transporters, pumps, and channels, some of which were identified …

Inorganic Polyphosphate Is in the Surface of Trypanosoma cruzi but Is Not Significantly Secreted

Trypanosoma cruzi is the etiologic agent of Chagas disease, an infection that can lead to the development of cardiac fibrosis, which is characterized by the deposition of extracellular matrix (ECM) components in the interstitial region of the myocardium. The parasite itself can induce myofibroblast differentiation of cardiac fibroblast in vitro, leading to increased expression of ECM. …

Two CTEGD trainees receive AHA fellowships

by Donna Huber   Baihetiya “Barna” Baierna, a cellular biology graduate student in Silvia Moreno’s laboratory, received an American Heart Association Pre-doctoral Fellowship. It will fund her training for the next two years as she studies the mitochondrion of Toxoplasma gondii. Baierna grew up wanting to follow in her mother’s footsteps as a scientist. “My …

Advances in the cellular biology, biochemistry, and molecular biology of acidocalcisomes

Acidocalcisomes are organelles conserved during evolution and closely related to the so-called volutin granules of bacteria and archaea, to the acidocalcisome-like vacuoles of yeasts, and to the lysosome-related organelles of animal species. All these organelles have in common their acidity and high content of polyphosphate and calcium. They are characterized by a variety of functions …