Mitochondria mechanosensing: The powerhouse fueling cellular force signaling

Current Biology, Journal Year: 2025, Volume and Issue: 35(2), P. R76 - R79

Published: Jan. 1, 2025

Language: Английский

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Extracellular matrix mechanical cues (dys)regulate metabolic redox homeostasis due to impaired autophagic flux

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Abstract Extracellular matrix (ECM) stiffness is increasingly recognized as a critical regulator of cellular behavior, governing processes such proliferation, differentiation, and metabolism. Neurodegenerative diseases are characterized by mitochondrial dysfunction, oxidative stress, impaired autophagy, progressive softening the brain tissue, yet research into how mechanical cues influence metabolism in this context remains scarce. In study, we evaluated long-term effects brain-compliant, soft ECM on bioenergetics, redox balance, autophagic capacity neuronal cells. Using human neuroblastoma (SH-SY5Y) mouse hippocampal (HT22) cell lines, well primary neurons, observed that prolonged exposure to resulted bioenergetic imbalance, disrupted flux. These findings were consistently validated across both Our data indicate decreased maximal cells exposed ECM, potentially due an imbalance autophagosome formation degradation, demonstrated LC3 II levels following chloroquine-induced flux inhibition. This impairment autophagy was coupled with increased further indicating metabolic alterations. emphasize role regulating suggest may mimic key aspects neurodegenerative disease pathology, thereby enhancing physiological relevance vitro models. study underscores necessity for mechanics contributing factor progression potential target therapeutic strategies.

Language: Английский

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Tension-induced organelle stress: an emerging target in fibrosis

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(4)

Published: Feb. 15, 2025

ABSTRACT Cells are continuously subjected to physical and chemical cues from the extracellular environment, sense respond mechanical via mechanosensation mechanotransduction. Although role of cytoskeleton in these processes is well known, contribution intracellular membranes has been long neglected. Recently, it become evident that various organelles play active roles both mechanosensing In this Review, we focus on mechanosensitive endoplasmic reticulum (ER), functions which crucial for maintaining cell homeostasis. We discuss effects stimuli interactions between ER, other organelles; ER Ca2+ signalling channels; how unfolded protein response lipid homeostasis contribute mechanosensing. The expansive structure positions as a key communication hub, additionally explore may be leveraged transduce signals around cell. By synthesising current knowledge, aim shed light emerging cellular

Language: Английский

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Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 12, 2025

Tumors often exhibit greater stiffness compared to normal tissues, primarily due increased deposition within the tumor stroma. Collagen, proteoglycans, laminin, and fibronectin are key components of extracellular matrix (ECM), interacting facilitate ECM assembly. Enhanced fiber density cross-linking result in elevated interstitial fluid pressure, subjecting tumors significant physical stress during growth. This mechanical is transduced intracellularly via integrins, Rho signaling pathway, Hippo thereby promoting invasion. Additionally, pressure fosters glycolysis cells, boosting energy production support metastasis. Mechanical cues also regulate macrophage polarization, maintaining an inflammatory microenvironment conducive survival. In summary, signals play a crucial role growth Understanding these their involvement progression essential for advancing our knowledge biology enhancing therapeutic approaches.

Language: Английский

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Piezo1 is a mechanosensor of soft matrix viscoelasticity

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Mechanosensitive ion channels, such as Piezo1, have emerged having fundamental roles in sensing the mechanical properties of extracellular matrix (ECM). However, whether and how Piezo1 senses time-dependent ECM properties, that is viscoelasticity, remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line which expression can be silenced with soft stiff viscoelastic hydrogels independently tuneable elastic viscous moduli. We demonstrate a mechanosensor viscoelasticity ECMs, both experimentally throughout simulations using modified molecular clutch model incorporates Piezo1. Using RNA sequencing, also identify transcriptomic phenotype MSC response to activity, identifying gene signatures modulate MSC’s mechanobiology hydrogels.

Language: Английский

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Emerging mechanobiology techniques to probe intracellular mechanics

npj Biological Physics and Mechanics., Journal Year: 2025, Volume and Issue: 2(1)

Published: April 4, 2025

Language: Английский

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Active control of mitochondrial network morphology by metabolism-driven redox state

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(16)

Published: April 17, 2025

Mitochondria are dynamic organelles that constantly change morphology. What controls mitochondrial morphology however remains unresolved. Using actively respiring yeast cells growing in distinct carbon sources, we find and activity unrelated. Cells can exhibit fragmented or networked different nutrient environments independent of activity. Instead, is controlled by the intracellular redox state, which itself depends on nature electron entry into transport chain (ETC)—through complex I/II directly to coenzyme Q/cytochrome c. In metabolic conditions where direct high, reactive oxygen species (ROS) increase, resulting an oxidized cytosolic environment rapid fragmentation. Decreasing ETC genetic chemical means, reducing rapidly restores morphologies. disruptions flow alter ROS demonstrate minute-scale, reversible control between forms activity-independent manner. Mechanistically, fission machinery through Dnm1 responds minute-scale state changes, preceding form. Thus, cell its consequent cellular

Language: Английский

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Macrophage response to fibrin structure mediated by Tgm2-dependent mitochondrial mechanosensing

Bioactive Materials, Journal Year: 2025, Volume and Issue: 50, P. 382 - 395

Published: April 22, 2025

Language: Английский

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Biophysical effects of Phellinus Linteus on hepatocellular carcinoma cells studied by atomic force microscopy

Journal of Photochemistry and Photobiology B Biology, Journal Year: 2025, Volume and Issue: 267, P. 113169 - 113169

Published: April 23, 2025

Language: Английский

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