Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis

Current Biology, Journal Year: 2023, Volume and Issue: 33(7), P. 1282 - 1294.e5

Published: March 9, 2023

The ongoing metabolic and microbicidal pathways that support protect cellular life generate potentially damaging reactive oxygen species (ROS). To counteract damage, cells express peroxidases, which are antioxidant enzymes catalyze the reduction of oxidized biomolecules. Glutathione peroxidase 4 (GPX4) is major hydroperoxidase specifically responsible for reducing lipid peroxides; this homeostatic mechanism essential, its inhibition causes a unique type lytic cell death, ferroptosis. mechanism(s) lead to lysis in ferroptosis, however, unclear. We report peroxides formed during ferroptosis accumulate preferentially at plasma membrane. Oxidation surface membrane lipids increased tension on led activation Piezo1 TRP channels. Oxidized membranes thus became permeable cations, ultimately leading gain Na+ Ca2+ concomitant with loss K+. These effects were reduced by deletion completely inhibited blocking cation channel conductance ruthenium red or 2-aminoethoxydiphenyl borate (2-APB). also found oxidation depressed activity Na+/K+-ATPase, exacerbating dissipation monovalent gradients. Preventing changes content attenuated Altogether, our study establishes permeability cations critical step execution identifies Piezo1, channels, Na+/K+-ATPase as targets/effectors death.

Language: Английский

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Vascular mechanotransduction

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(2), P. 1247 - 1421

Published: Jan. 5, 2023

This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial (ECs), including their sensing mechanical stimuli transduction signals that result acute functional modulation longer-term transcriptomic epigenetic regulation blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures receptors, junction proteins. mechanosignaling pathways presented cytoskeleton, integrins, extracellular matrix, intracellular signaling molecules. These are followed by discussions on transcriptome epigenetics, relevance health disease, interactions between VSMCs ECs. Throughout this review, we offer suggestions for specific topics require further understanding. In closing section conclusions perspectives, summarize what is known point out need treat vasculature as a system, not only ECs but also matrix other types such resident macrophages pericytes, so can fully understand physiology pathophysiology vessel whole, thus enhancing comprehension, diagnosis, treatment, prevention diseases.

Language: Английский

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Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions

Neuron, Journal Year: 2022, Volume and Issue: 110(18), P. 2984 - 2999.e8

Published: Aug. 12, 2022

Language: Английский

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Synthetic Biology: Bottom-Up Assembly of Molecular Systems

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(21), P. 16294 - 16328

Published: Sept. 30, 2022

The bottom-up assembly of biological and chemical components opens exciting opportunities to engineer artificial vesicular systems for applications with previously unmet requirements. modular combination scaffolds functional building blocks enables the engineering complex biomimetic or new-to-nature functionalities. Inspired by compartmentalized organization cells organelles, lipid polymer vesicles are widely used as model membrane investigate translocation solutes transduction signals proteins. functionalization such compartments full control over their composition can thus provide specifically optimized environments synthetic processes. This review aims inspire future endeavors providing a diverse toolbox molecular modules, methodologies, different approaches assemble systems. Important technical practical aspects addressed selected presented, highlighting particular achievements limitations approach. Complementing cutting-edge technological achievements, fundamental also discussed cater inherently background target audience, which results from interdisciplinary nature biology. proteins modules use lipids block copolymers scaffold functionalized explored in detail. Particular emphasis is placed on ensuring controlled these into increasingly Finally, all descriptions presented greater context valuable biocatalysis, biosensing, bioremediation, targeted drug delivery.

Language: Английский

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Direct observation of the conformational states of PIEZO1

Nature, Journal Year: 2023, Volume and Issue: 620(7976), P. 1117 - 1125

Published: Aug. 16, 2023

Abstract PIEZOs are mechanosensitive ion channels that convert force into chemoelectric signals 1,2 and have essential roles in diverse physiological settings 3 . In vitro studies proposed PIEZO transduce mechanical through the deformation of extensive blades transmembrane domains emanating from a central ion-conducting pore 4–8 However, little is known about how these interact with their native environment which molecular movements underlie activation. Here we directly observe conformational dynamics individual PIEZO1 molecules cell using nanoscopic fluorescence imaging. Compared previous structural models PIEZO1, show significantly expanded at rest by bending stress exerted plasma membrane. The degree expansion varies dramatically along length blade, where decreased binding strength between subdomains can explain increased flexibility distal blade. Using chemical modulators blade channel activation correlated. Our findings begin to uncover activated environment. More generally, as reliably detect shifts single nanometres populations channels, expect this approach will serve framework for analysis membrane proteins

Language: Английский

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Membrane protein isolation and structure determination in cell-derived membrane vesicles

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(18)

Published: April 25, 2023

Integral membrane protein structure determination traditionally requires extraction from cell membranes using detergents or polymers. Here, we describe the isolation and of proteins in vesicles derived directly cells. Structures ion channel Slo1 total plasma were determined at 3.8 Å 2.7 resolution, respectively. The environment stabilizes Slo1, revealing an alteration global helical packing, polar lipid, cholesterol interactions that stabilize previously unresolved regions additional binding site Ca

Language: Английский

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Mechanical activation opens a lipid-lined pore in OSCA ion channels

Nature, Journal Year: 2024, Volume and Issue: 628(8009), P. 910 - 918

Published: April 3, 2024

Language: Английский

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Mechanisms of mechanotransduction and physiological roles of PIEZO channels

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

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How plants sense and respond to osmotic stress

Journal of Integrative Plant Biology, Journal Year: 2024, Volume and Issue: 66(3), P. 394 - 423

Published: Feb. 8, 2024

ABSTRACT Drought is one of the most serious abiotic stresses to land plants. Plants sense and respond drought stress survive under water deficiency. Scientists have studied how plants stress, or osmotic caused by drought, ever since Charles Darwin, gradually obtained clues about sensing signaling in Osmotic a physical stimulus that triggers many physiological changes at cellular level, including turgor, cell wall stiffness integrity, membrane tension, fluid volume, may some these stimuli trigger downstream responses. In this review, we emphasized potential movements organisms, compared putative signal inputs wall‐containing wall‐free prospected volume according advances plants, animals, yeasts, bacteria, summarized multilevel biochemical outputs, such as plasma nanodomain formation, permeability, root hydrotropism, halotropism, Casparian strip suberin lamellae, finally proposed hypothesis responses are likely be cocktail mediated multiple osmosensors. We also discussed core scientific questions, provided perspective future directions field, highlighted importance robust smart systems efficient source‐sink allocations for generating high‐yield stress‐resistant crops

Language: Английский

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PIEZO Ion Channels in Cardiovascular Functions and Diseases

Circulation Research, Journal Year: 2024, Volume and Issue: 134(5), P. 572 - 591

Published: Feb. 29, 2024

The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells tissues. Thus, this primed with mechanosensory structures that respond adapt changes in stimuli. Since their discovery 2010, PIEZO ion channels have dominated field of mechanobiology. These been proposed long-sought-after mechanosensitive excitatory involved touch proprioception mammals. However, more pieces evidence point importance activities disease development. channel-related cardiac functions include transducing hemodynamic endothelial vascular cells, red cell homeostasis, platelet aggregation, arterial pressure regulation, among others. contribute pathological conditions including hypertrophy pulmonary hypertension congenital syndromes generalized lymphatic dysplasia xerocytosis. In review, we highlight recent advances understanding role diseases. Achievements quickly expanding should open a new road for efficient control PIEZO-related diseases functions.

Language: Английский

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