Nuclear metabolism oscillation during the cell cycle reveals a link between the phosphatidylinositol pathway and histone methylation DOI Open Access
Antoni Gañez Zapater, Savvas Kourtis, Lorena Espinar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The progression of the cell cycle is regulated by expression specific genes and fluctuations in cellular metabolic states. Previous research has employed cycle-based transcriptomics, proteomics, metabolomics analyses to identify cycle-dependent changes at gene expression, protein, levels. However, role protein compartmentalization regulating function, coupled with evidence that enzymes can localize nucleus influence chromatin states, suggests nuclear metabolism may play a progression. In this study, we developed an approach resolve during unbiased systematic manner. This was achieved integrating fluorescent reporters mass spectrometry imaging. Our investigation focused on revealed phosphatidylinositol localizes Moreover, disruption affects distribution 4,5-bisphosphate, alters number morphology nucleoli, influences maintenance distinct heterochromatin states throughout cycle. Finally, given established link between methionine synthesis, as well differential impact observed histone marks when perturbed, proposed pools be involved decorate

Language: Английский

Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration DOI
Laura R. Lee, Bruno Guillotin, Ramin Rahni

et al.

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

5

The potential influence of melatonin on mitochondrial quality control: a review DOI Creative Commons
Xudan Lei,

Zhenni Xu,

Lingxiao Huang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of homeostasis functional recovery after injury coordinated by biogenesis, dynamics autophagy, which collectively referred to as quality control. There increasing evidence that mitochondria important targets melatonin exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported metabolized in mitochondria. In this review, we summarize the role damaged elimination energy supply regulating control, may provide new strategies clinical treatment mitochondria-related diseases.

Language: Английский

Citations

11

Prunin: An Emerging Anticancer Flavonoid DOI Open Access
Juie Nahushkumar Rana, Sohail Mumtaz

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2678 - 2678

Published: March 16, 2025

Despite the substantial advances in cancer therapies, developing safe and effective treatment methodologies is critical. Natural (plant-derived compounds), such as flavonoids, might be crucial a methodology without toxicity toward healthy tissues. Prunin flavonoid with potential to used biomedical applications. has yet undergo thorough scientific research, its precise molecular mechanisms of action remain largely unexplored. This review summarizes therapeutic prunin for first time, focusing on underlying an anticancer compound. gained significant attention due antioxidant, anti-inflammatory, effects. aims unlock how functions at level exert effects, primarily modulating key cellular pathways. Furthermore, we have discussed prunin’s adjunctive therapy conventional treatments, highlighting ability strengthen responses while decreasing drug resistance. Moreover, discussion probes into innovative delivery methods, particularly nanoformulations, that address bioavailability, solubility, stability limitations optimize application. By providing comprehensive analysis properties, this stimulate further exploration using agent, thereby progressing development targeted, selective, safe, methods.

Language: Английский

Citations

1

Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome cell models through transcriptomic and proteomic analysis DOI Creative Commons
R.E. Jones, Elaine A. Dunlop,

Jesse D. Champion

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Abstract Birt-Hogg-Dubé syndrome (BHD) patients are uniquely susceptible to all renal tumor subtypes. However, the underlying mechanism of carcinogenesis is unclear. To study cancer development in BHD, we used human proximal kidney (HK2) cells and found that long-term folliculin ( FLCN ) knockdown was required increase tumorigenic potential these cells, as evidenced by formation larger spheroids under nonadherent conditions. Transcriptomic proteomic analyses revealed links between FLCN, cell cycle control DNA damage response (DDR) machinery. In addition, HK2 lacking had an altered transcriptome profile enriched genes. G 1 /S checkpoint signaling compromised increased protein levels cyclin D1 (CCND1) hyperphosphorylation retinoblastoma (RB1). A interactome screen binds DNA-dependent kinase (DNA-PK). This novel interaction reversed irradiation-responsive manner. Knockdown caused a marked γH2AX RB1 phosphorylation. The both CCND1 phosphorylated remained high during damage, which associated with defective knockdown. Furthermore, Flcn -knockdown C. elegans were arrest damage. work loss defects BHD could contribute their risk cancer.

Language: Английский

Citations

1

Mitochondria – the CEO of the cell DOI
Laurie Lee-Glover, Martin Picard, Timothy E. Shutt

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(9)

Published: May 1, 2025

As we have learned more about mitochondria over the past decades, including their essential cellular roles and how altered mitochondrial biology results in disease, it has become apparent that they are not just powerplants pumping out ATP at whim of cell. Rather, dynamic information energy processors play crucial directing dozens processes behaviors. They provide instructions to enact programs regulate various operations, such as complex metabolic networks, signaling innate immunity, even control cell fate, dictating when cells should divide, differentiate or die. To help current future generations biologists incorporate dynamic, multifaceted nature assimilate modern discoveries into scientific framework, need a 21st century 'rebranding'. In this Opinion article, argue be considered 'Chief Executive Organelle' - CEO

Language: Английский

Citations

1

The clock-like accumulation of germline and somatic mutations can arise from the interplay of DNA damage and repair DOI Creative Commons
Natanael Spisak, Marc de Manuel, William Milligan

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(6), P. e3002678 - e3002678

Published: June 17, 2024

The rates at which mutations accumulate across human cell types vary. To identify causes of this variation, are often decomposed into a combination the single-base substitution (SBS) “signatures” observed in germline, soma, and tumors, with idea that each signature corresponds to one or small number underlying mutagenic processes. Two such signatures turn out be ubiquitous types: SBS 1, consists primarily transitions methylated CpG sites thought caused by spontaneous deamination, more diffuse 5, is unknown etiology. In cancers, attributed these 2 accumulates linearly age diagnosis, thus have been termed “clock-like.” better understand clock-like behavior, we develop mathematical model includes DNA replication errors, unrepaired damage, damage repaired incorrectly. We show mutational can exhibit behavior because divisions occur constant rate and/or remain over time, distinct sources teased apart comparing lineages divide different rates. With goal mind, analyze accumulation multiple types, including soma as well male female germline. find no detectable increase 1 neurons only very weak assigned but significant time rapidly dividing cells, suggesting driven rounds occurring relatively fixed rate. contrast, 5 increases all postmitotic ones, indicating it independently divisions; observation points errors repair key mechanism. Thus, two “clock-like” likely origins, set division, other

Language: Английский

Citations

8

mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction DOI Creative Commons
Jay N. Joshi,

Ariel D. Lerner,

Frank Scallo

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114543 - 114543

Published: July 26, 2024

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that active in nearly all proliferating eukaryotic cells; however, it unclear whether mTORC1 activity changes throughout the cell cycle. We find oscillates from lowest mitosis/G1 to highest S/G2. The interphase oscillation mediated through TSC complex but independent major known regulatory inputs, including Akt and Mek/Erk signaling. By contrast, suppression mitosis does not require complex. has long been promote progression G1. also promotes S G2 important for satisfying Chk1/Wee1-dependent G2/M checkpoint allow entry into mitosis. low G1 sensitizes cells autophagy induction response partial inhibition or reduced nutrient levels. Together, these findings demonstrate differentially regulated cycle, with phase-specific consequences cells.

Language: Английский

Citations

5

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition DOI Creative Commons
Huihui Zhao, Xinxin Cheng, Liping Yan

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 23, 2024

Abstract Background In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported be involved regulating multiple metabolic processes by facilitating ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation pathway utilized tumor cells that crucial for malignant progression; however, its association with APC/C remains explored. Methods Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed investigate carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay co-immunoprecipitation detect interactions between CPT1C APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch transwell assays xenograft transplantation role progression vitro vivo. Immunohistochemistry was on tissue microarray evaluate levels explore potential clinical value. Results We identified novel substrate. protein exhibited cycle-dependent fluctuations, peaking at G1/S boundary. Elevated accelerated transition, proliferation Furthermore, enhanced fatty utilization, upregulated ATP levels, decreased reactive oxygen species thereby favoring survival harsh environment. Clinically, high correlated poor patients esophageal squamous carcinoma. Conclusions Overall, our results revealed interplay utilization machinery cells. Additionally, promoted augmenting cellular preserving redox homeostasis, particularly under stress. Therefore, could an independent prognostic indicator

Language: Английский

Citations

4

Autonomous living materials and bone-inspired scaffolds motivated by human osteogenic microenvironment mechanisms DOI Creative Commons
Yutong Chen, Seeram Ramakrishna,

Zhengyang Jin

et al.

Materials & Design, Journal Year: 2024, Volume and Issue: 244, P. 113145 - 113145

Published: July 8, 2024

The repair of secondary critical bone defects is an international medical challenge. Bone tissue engineering provides methods and technology for repair. regeneration mechanism serves as inspiration the material structural design scaffolds. In terms materials, this review draws from biological characteristics host cells in osteogenic microenvironment (including osteoblast lineage, vascular cell inflammatory cells, etc.), reviewing regulatory mechanisms self-healing proposing autonomous living materials scaffolds which prepared by in-situ manufacturing. Autonomous regulate migration, proliferation differentiation real time releasing steadily long-term. Regarding structure, we functional role natural structures homeostasis, providing insights into bone-inspired Due to conflict between mechanical properties ability, proposes assembled They can prolong half-life provide support attachment points new growth, autonomously microenvironment. have potential advance research progress field pave way novel clinical treatments.

Language: Английский

Citations

4

Precise Electromagnetic Modulation of the Cell Cycle and Its Applications in Cancer Therapy DOI Open Access
K. Shi,

Xiqing Peng,

Ting Xu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4445 - 4445

Published: May 7, 2025

Precise modulation of the cell cycle via electromagnetic (EM) control presents a groundbreaking approach for cancer therapy, especially in development personalized treatment strategies. EM fields can precisely regulate key cellular homeostatic mechanisms such as proliferation, apoptosis, and repair by finely tuning parameters like frequency, intensity, duration. This review summarizes through which influence dynamics, highlighting recent developments high-throughput platforms that facilitate precise regulation. Additionally, integration with emerging technologies artificial intelligence, immunotherapy, nanotechnology is explored, collectively enhancing targeting precision, immune activation, therapeutic efficacy. A systematic analysis existing clinical studies indicates technology significantly overcomes challenges tumor heterogeneity, microenvironment complexity, treatment-related adverse effects. prospects translation future research directions, emphasizing its critical potential core element individualized multimodal

Language: Английский

Citations

0