Mechanisms and functions of protein S-acylation

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 488 - 509

Published: Feb. 14, 2024

Language: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(4), P. 1899 - 1949

Published: Feb. 8, 2024

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, energy status, influences structure cytoplasm thereby indirectly function. Notably, also promotes formation biomolecular condensates by phase separation, initially identified eukaryotic cells but more recently discovered to play key functions Bacterial require a variety mechanisms maintain homeostasis, particular environments fluctuating conditions, is emerging one mechanism. In this work, we connect homeostasis function bacterial cell compare supramolecular structures found bacteria those cells. We focus on effects separation control chromosome replication, segregation, division, discuss contribution fitness adaptation environmental stress.

Language: Английский

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Endoplasmic reticulum: Monitoring and maintaining protein and membrane homeostasis in the endoplasmic reticulum by the unfolded protein response

The International Journal of Biochemistry & Cell Biology, Journal Year: 2024, Volume and Issue: 172, P. 106598 - 106598

Published: May 18, 2024

The endoplasmic reticulum (ER) regulates essential cellular processes, including protein folding, lipid synthesis, and calcium homeostasis. ER homeostasis is maintained by a conserved set of signaling cascades called the Unfolded Protein Response (UPR). How UPR senses perturbations in has been subject active research for decades. In metazoans, consists three ER-membrane embedded sensors: IRE1, PERK ATF6. These sensors detect accumulation misfolded proteins lumen adjust folding capacity according to needs. Early work revealed that ER-resident chaperone BiP binds all higher eukaryotes binding was suggested regulate their activity. More recent data have shown interaction with complex network chaperones modulates activation deactivation dynamics. Furthermore, emerging evidence suggests monitors membrane integrity beyond defects. However, mechanistic structural basis proteotoxic bilayer stress remains only partially understood. Here, we review current understanding novel networks contribution environment activation.

Language: Английский

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Membrane localization accelerates association under conditions relevant to cellular signaling

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(10)

Published: March 1, 2024

Translocation of cytoplasmic molecules to the plasma membrane is commonplace in cell signaling. Membrane localization has been hypothesized increase intermolecular association rates; however, it also argued that should be faster cytosol because diffusion slow. Here, we directly compare an identical reaction, binding complementary DNA strands, solution and on supported membranes. The measured rate constants show for a 10-µm-radius spherical cell, 22- 33-fold at than cytoplasm. kinetic advantage depends size essentially negligible typical ~1 µm prokaryotic cells. enhancement attributable combination higher encounter rates two dimensions reaction probability per encounter.

Language: Английский

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Osmotic Pressure and Its Biological Implications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3310 - 3310

Published: March 14, 2024

Gaining insight into osmotic pressure and its biological implications is pivotal for revealing mechanisms underlying numerous fundamental processes across scales will contribute to the biomedical pharmaceutical fields. This review aims provide an overview of current understanding, focusing on two central issues: (i) how determine theoretically (ii) affects important activities. More specifically, we discuss representative theoretical equations models different solutions, emphasizing their applicability limitations, summarize effect lipid phase separation, cell division, differentiation, dependence these processes. We highlight that new theory applicable all experimentally feasible temperatures solute concentrations needs be developed, further studies regarding role in other should also carried out improve our comprehensive in-depth understanding. Moreover, point importance challenges developing techniques vivo measurement pressure.

Language: Английский

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Role of lipoprotein structure and dynamics in disease development: from atherosclerosis to Covid-19

Published: Jan. 1, 2023

Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such cholesterol and triglycerides the bloodstream. Atherosclerosis is complex cardiovascular disease characterized by accumulation of cholesterol-rich plaques arterial walls, leading to narrowed hardened arteries. Recently, spike protein from SARS-CoV-2 virus, responsible COVID-19, has been subject research concerning its potential impact on metabolism association with disease. Understanding interaction between lipoproteins influence could have implications our knowledge health. In this research, we investigated ultrastructure HDL individuals different profiles well mature model nascent membranes. these differences will help create novel rHDL particles superior lipid-removing CVD-treating properties. Finally, cell membranes study imbalances metabolism. To achieve objectives, deposition, exchange removal were followed techniques Neutron reflection attenuated total Fourier transformation infrared spectroscopy while, was unravelled small-angle X-ray scattering.

Language: Английский

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Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

The cell surface proteome, or surfaceome, is the hub for cells to interact and communicate with outside world. Many disease-associated changes are hard-wired within yet approved drugs target less than 50 proteins. In past decade, proteomics community has made significant strides in developing new technologies tailored studying surfaceome all its complexity. this review, we first dive into unique characteristics functions of emphasizing necessity specialized labeling, enrichment, proteomic approaches. An overview surfaceomics methods provided, detailing techniques measure protein expression how leads novel discovery. Next, highlight advances proximity labeling (PLP), showcasing various enzymatic photoaffinity can map protein-protein interactions membrane complexes on surface. We then review role extracellular post-translational modifications, focusing glycosylation, proteolytic remodeling, secretome. Finally, discuss identifying tumor-specific peptide MHC they have shaped therapeutic development. This emerging field neo-protein epitopes constantly evolving, where targets identified at proteome level encompass defined PTMs, complexes, dysregulated cellular tissue locations. Given functional importance biology therapy, view as a critical piece quest neo-epitope

Language: Английский

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Mass Photometry

Annual Review of Biophysics, Journal Year: 2025, Volume and Issue: 54(1), P. 379 - 399

Published: May 6, 2025

Mass photometry (MP) is a technology for the mass measurement of biological macromolecules in solution. Its accuracy and resolution have transformed label-free optical detection into quantitative measurement, enabling identification distinct species mixture characterization their relative abundances. applicability to variety biomolecules, including polypeptides, nucleic acids, lipids, sugars, coupled with ability quantify heterogeneity, interaction energies, kinetics, has driven rapid widespread adoption MP across life sciences community. These applications been largely orthogonal those traditionally associated microscopy, such as detection, imaging, tracking, instead focusing on constituents biomolecular complexes change time. Here, we present an overview origins MP, its current applications, future improvements that will further expand scope.

Language: Английский

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A dynamic duo: Understanding the roles of FtsZ and FtsA for Escherichia coli cell division through in vitro approaches

European Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 103(1), P. 151380 - 151380

Published: Dec. 28, 2023

Bacteria divide by binary fission. The protein machine responsible for this process is the divisome, a transient assembly of more than 30 proteins in and on surface cytoplasmic membrane. Together, they constrict cell envelope remodel peptidoglycan layer to eventually split into two. For Escherichia coli, most molecular players involved have probably been identified, but obtaining quantitative information needed mechanistic understanding can often not be achieved from experiments vivo alone. Since discovery Z-ring years ago, vitro reconstitution crucial shed light processes normally hidden complex environment living cell. In review, we summarize how rebuilding divisome purified components - or at least parts it instrumental obtain detailed bacterial division machinery that today.

Language: Английский

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