Recently, rapid progress in our structural knowledge of K(+)-selective channels has started to provide a basis for comprehending the biophysical machinery underlying their electrophysiological properties. These studies have begun to reveal how a diverse array of distinct, cytoplasmically positioned domains affect the activity of associated channels. Some of these establish functional diversity by selectively mediating channel assembly. More importantly, these cytoplasmic domains couple intracellular signals to the gating of their associated pore. New structural insights are providing a clearer understanding of the fundamental molecular mechanisms of these K(+) channels that, in turn, partly underlie complex neurological phenomena.
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http://dx.doi.org/10.1016/j.tibs.2003.11.008 | DOI Listing |
Commun Biol
November 2024
Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK.
Plasmodium male and female gametocytes are the gatekeepers of human-to-mosquito transmission, therefore essential for propagation of malaria within a population. Whilst dormant in humans, their divergent roles during transmission become apparent soon after mosquito feeding with a rapid transformation into gametes - males forming eight motile sperm-like cells aiming to fertilise a single female gamete. Little is known about how the parasite fuels this abrupt change, and the potential role played by their large and elaborate cristate mitochondrion.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.
malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, requires nutritional iron to support essential metabolic pathways, but the critical mechanisms of iron acquisition and trafficking during RBC infection have remained obscure. Parasites internalize and liberate massive amounts of heme during large-scale digestion of RBC hemoglobin within an acidic food vacuole (FV) but lack a heme oxygenase to release porphyrin-bound iron.
View Article and Find Full Text PDFBiomolecules
October 2024
National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health.
View Article and Find Full Text PDFPLoS One
October 2024
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
The voltage-dependent anion channel 1 (VDAC1) is a crucial gatekeeper in the outer mitochondrial membrane, controlling metabolic and energy homeostasis. The available methodological approaches fell short of accurate visualization of VDAC1 in living cells. To permit precise VDAC1 imaging, we utilized the tetracysteine (TC)-tag and visualized VDAC1 dynamics in living cells.
View Article and Find Full Text PDFMethods Cell Biol
October 2024
University of Zaragoza/Aragón Health Research Institute, Biochemistry and Molecular and Cell Biology, Zaragoza, Spain. Electronic address:
At odds with historical views suggesting that mitochondrial functions are largely dispensable for cancer cells, it is now clear that mitochondria have a major impact on malignant transformation, tumor progression and response to treatment. Mitochondria are indeed critical for neoplastic cells not only as an abundant source of ATP and other metabolic intermediates, but also as gatekeepers of apoptotic cell death and inflammation. Interestingly, while mitochondrial components are mostly encoded by nuclear genes, mitochondria contain a small, circular genome that codes for a few mitochondrial proteins, ribosomal RNAs and transfer RNAs.
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