In-Cell Structural Biology by NMR: The Benefits of the Atomic Scale

Chemical Reviews, Год журнала: 2022, Номер 122(10), С. 9497 - 9570

Опубликована: Март 31, 2022

In-cell structural biology aims at extracting information about proteins or nucleic acids in their native, cellular environment. This emerging field holds great promise and is already providing new facts outlooks of interest both fundamental applied levels. NMR spectroscopy has important contributions on this stage: It brings a broad variety nuclei the atomic scale, which ensures its versatility uniqueness. Here, we detail methods, knowledge, applications biomedical engineering related to in-cell by NMR. We finally propose brief overview main other techniques (EPR, smFRET, cryo-ET, etc.) draw some advisable developments for In era large-scale screenings deep learning, accurate qualitative experimental evidence are as essential ever understand interior life cells. can generate such it does so scale. review meant deliver comprehensive but accessible information, with advanced technical details reflections nature results, future field.

Язык: Английский

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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Genes & Diseases, Год журнала: 2023, Номер 11(1), С. 189 - 204

Опубликована: Янв. 14, 2023

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology, as it represents a major obstacle to effective cancer treatment. Since cells are highly diverse at genetic, epigenetic, and phenotypic levels, intra-tumor can be assumed an important contributing factor nullification chemotherapeutic effects, recurrence tumor. Based on role heterogeneous subpopulations with varying cell-cycle dynamics behavior during progression treatment; herein, we aim establish comprehensive definition for adaptation neoplastic against therapy. We discuss two parallel yet distinct that play pivotal roles reducing effects chemotherapy: "resistant" "tolerant" populations. Furthermore, this review also highlights impact quiescent phase cell cycle survival mechanism cells. Beyond understanding mechanisms underlying quiescence, provides insightful perspective stem (CSCs) their dual intertwined functions based state response Moreover, CSCs, epithelial–mesenchymal transformed cells, circulating (CTCs), disseminated (DTCs), which mostly proved have multiple biological links implicated our viewpoint tumors. Overall, increasing knowledge key identifying new therapeutic solutions, emerging concept may provide us opportunities prevent dreadful recurrence.

Язык: Английский

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Gene expression during the formation of resting spores induced by nitrogen starvation in the marine diatom Chaetoceros socialis

BMC Genomics, Год журнала: 2023, Номер 24(1)

Опубликована: Март 10, 2023

Dormancy is widespread in both multicellular and unicellular organisms. Among diatoms, microalgae at the base of all aquatic food webs, several species produce dormant cells (spores or resting cells) that can withstand long periods adverse environmental conditions.We present first gene expression study during process spore formation induced by nitrogen depletion marine planktonic diatom Chaetoceros socialis. In this condition, genes related to photosynthesis nitrate assimilation, including high-affinity transporters (NTRs), were downregulated. While former result a common reaction among diatoms under stress, latter seems be exclusive spore-former C. The upregulation catabolic pathways, such as tricarboxylic acid cycle, glyoxylate cycle fatty beta-oxidation, suggests could use lipids source energy formation. Furthermore, lipoxygenase aldehyde dehydrogenases (ALDHs) advocates presence oxylipin-mediated signaling, while involved dormancy-related pathways conserved other organisms (e.g. serine/threonine-protein kinases TOR its inhibitor GATOR) provides interesting avenues for future explorations.Our results demonstrate transition from an active growth phase one characterized marked metabolic changes evidence signaling intercellular communication.

Язык: Английский

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Hypometabolism to survive the long polar night and subsequent successful return to light in the diatom Fragilariopsis cylindrus

New Phytologist, Год журнала: 2023, Номер 241(5), С. 2193 - 2208

Опубликована: Дек. 14, 2023

Diatoms, the main eukaryotic phytoplankton of polar marine regions, are essential for maintenance food chains specific to Arctic and Antarctic ecosystems, experiencing major disturbances under current climate change. As such, it is fundamental understand physiological mechanisms associated molecular basis their endurance during long night. Here, using diatom Fragilariopsis cylindrus, we report an integrative analysis combining transcriptomic, microscopic biochemical approaches shed light on strategies used survive We reveal that in prolonged darkness, cells enter a state quiescence with reduced metabolic transcriptional activity, which no cell division occurs. propose minimal energy provided by respiration degradation protein, carbohydrate lipid stores homeostasis maintained autophagy darkness. also internal structural changes manifest morphological acclimation including appearance large vacuole. Our results further show immediately following return light, able use photoprotective rapidly resume photosynthesis, demonstrating remarkable robustness diatoms darkness at low temperature.

Язык: Английский

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Nuclear Hsp104 safeguards the dormant translation machinery during quiescence

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 5, 2024

Abstract The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic biosynthesis system. Here, we find age-associated metabolic cues target yeast disaggregase Hsp104 to maintain functional nuclear proteome during quiescence. switch respiratory metabolism accompanying decrease in translation rates direct interact latent initiation factor eIF2 suppress aggregation. Hindering from entering quiescent cells results delayed re-entry into cell cycle due compromised resumption synthesis. In sum, report cytosolic-nuclear partitioning is critical mechanism protect synthesis machinery quiescence yeast, ensuring rapid restart once nutrients are replenished.

Язык: Английский

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A Key Role of the EMC Complex for Mitochondrial Respiration and Quiescence in Fission Yeasts

Yeast, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

ABSTRACT In eukaryotes, oxygen consumption is mainly driven by the respiratory activity of mitochondria, which generates most cellular energy that sustains life. This parameter provides direct information about mitochondrial all aerobic biological systems. Using Seahorse analyzer instrument, we show here deletion oca3/emc2 gene ( oca3Δ ) encoding Emc2 subunit ER membrane complex (EMC), a conserved chaperone/insertase aids protein biogenesis in ER, severely affects rates and quiescence survival Schizosaccharomyces pombe yeast cells. Remarkably, defect mutation (EMC dysfunction) rescued synergistically disruption ergosterol biosynthesis erg5Δ) action fluidizing agent tween 20, suggesting role fluidity sterol composition respiration fission yeast.

Язык: Английский

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The characteristics of differentiated yeast subpopulations depend on their lifestyle and available nutrients

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 14, 2024

Abstract Yeast populations can undergo diversification during their growth and ageing, leading to the formation of different cell-types. Differentiation into two major subpopulations, differing in cell size density exhibiting distinct physiological metabolic properties, was described planktonic liquid cultures colonies growing on semisolid surfaces. Here, we compare stress resistance, metabolism expression marker genes seven differentiated subpopulations emerging cultivation fermentative or respiratory media colony development same type solid media. The results show that more-dense are more resistant than less-dense under all conditions tested. On other hand, capacity, enzymatic activities gene differed between subpopulations. These characteristics influenced by lifestyle population (colony vs. cultivation) medium composition. Only medium, do not form as tested, but cells exhibit a range This suggests signals for differentiation may be triggered prior reprogramming an unknown signal from structured environment colony.

Язык: Английский

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Premature aging in aneuploid yeast is caused in part by aneuploidy-induced defects in Ribosome Quality Control

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 23, 2024

Premature aging is a hallmark of Down syndrome, caused by trisomy human chromosome 21, but the reason unclear and difficult to study in humans. We used an aneuploid model wild yeast show that amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, healthy aging, across genetic backgrounds amplified chromosomes. discovered these defects are due part aneuploidy-induced dysfunction Ribosome Quality Control (RQC). Compared euploids, aneuploids entering display aberrant ribosome profiles, accumulate RQC intermediates, harbor increased load protein aggregates. Although they have normal proteasome capacity, signs ubiquitin dysregulation, which impacts cyclin abundance disrupt arrest. Remarkably, inducing stalling euploids produces similar aberrations, while up-regulating limiting subunits or proteins metabolism alleviates many defects. Our results provide implications for other aneuploidy disorders including syndrome.

Язык: Английский

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Phenotypic heterogeneity follows a growth-viability tradeoff in response to amino acid identity

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 2, 2024

Abstract In their natural environments, microorganisms mainly operate at suboptimal growth conditions with fluctuations in nutrient abundance. The resulting cellular adaptation is subject to conflicting tasks: or survival maximisation. Here, we study this by systematically measuring the impact of a nitrogen downshift 24 sources on metabolism single-cell level. Saccharomyces lineages grown rich media and exposed gradually differentiate form two subpopulations different cell sizes where one favours while other viability an extended chronological lifespan. This differentiation asymmetrical daughter cells representing new differentiated state increased viability. We characterise metabolic response using RNA sequencing, biosensors transcription factor-tagged GFP library coupled high-throughput microscopy, imaging more than 800,000 cells. find that subpopulation associated dormant quiescent displaying differences MAPK signalling. Depending identity source present, into can be actively maintained, attenuated, aborted. These results establish amino acids as important signalling molecules for formation genetically identical subpopulations, involved lifespan rate determination.

Язык: Английский

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Transcription factor networks in cellular quiescence

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Язык: Английский

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