Metabolic regulation of proteome stability via N-terminal acetylation controls male germline stem cell differentiation and reproduction DOI Creative Commons
Charlotte M. François, Thomas Pihl, Marion Dunoyer de Segonzac

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 23, 2023

Abstract The molecular mechanisms connecting cellular metabolism with differentiation remain poorly understood. Here, we find that metabolic signals contribute to stem cell and germline homeostasis during Drosophila melanogaster spermatogenesis. We discovered external citrate, originating outside the gonad, fuels production of Acetyl-coenzyme A by ATP-citrate lyase (dACLY). show this pathway is essential final spermatogenic stages, where a high level promotes NatB-dependent N-terminal protein acetylation. Using genetic biochemical experiments, establish acetylation shields key target proteins, for spermatid differentiation, from proteasomal degradation ubiquitin ligase dUBR1. Our work uncovers crosstalk between proteome stability mediated via post-translational modification. propose system coordinates state organism gamete production. More broadly, modulation turnover circulating metabolites may be conserved regulatory mechanism control functions.

Language: Английский

The protective effect of Enteromorpha prolifera polysaccharide on alcoholic liver injury in C57BL/6 mice DOI
Tingting Yan, Yuying Zhang, Hengyu Lu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 261, P. 129908 - 129908

Published: Feb. 4, 2024

Language: Английский

Citations

22
Effects of lipid levels on growth performance and glucose and lipid metabolism of adult Nile tilapia (Oreochromis niloticus) fed with high carbohydrate diets DOI
Ningning Xie,

Jianmin Zhang,

Ming Jiang

et al.

Aquaculture Reports, Journal Year: 2025, Volume and Issue: 40, P. 102639 - 102639

Published: Jan. 18, 2025

Language: Английский

Citations

2
Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment DOI Creative Commons
Russel J. Reıter, Ramaswamy Sharma, Walter Manucha

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102480 - 102480

Published: Sept. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Language: Английский

Citations

13
The role of metabolites in the progression of osteoarthritis: Mechanisms and advances in therapy DOI Creative Commons
Xiaofeng Liu, Yongqiang Zheng, Zhengwei Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 56 - 70

Published: Jan. 1, 2025

Osteoarthritis (OA) is a progressive degenerative disease affected by many factors, and there currently no effective treatment. In recent years, the latest progress in metabolomics OA research has revealed several metabolic pathways new specific metabolites involved OA. Metabolites play significant roles identification management of This review looks back on development history this technology as well its potential clinical applications. It summarizes applications field future directions. understanding will advance treatment goals for The offers possibilities article reviews relationship between associated with chondrocytes Selectively altering these three their may hold great focal points

Language: Английский

Citations

1
Microbes in water treatment process DOI

Jeffrey Saúl Cedeño-Muñoz,

Bryan Fernando Rivadeneira-Mendoza, Luis Ángel Zambrano-Intriago

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 255 - 277

Published: Jan. 1, 2025

Language: Английский

Citations

1
Acetyl-CoA metabolism as a therapeutic target for cancer DOI Open Access
Guo Chen, Banghe Bao, Cheng Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115741 - 115741

Published: Oct. 19, 2023

Acetyl-coenzyme A (acetyl-CoA), an essential metabolite, not only takes part in numerous intracellular metabolic processes, powers the tricarboxylic acid cycle, serves as a key hub for biosynthesis of fatty acids and isoprenoids, but also signaling substrate acetylation reactions post-translational modification proteins, which is crucial epigenetic inheritance cells. Acetyl-CoA links lipid metabolism with histone to create more intricate regulatory system that affects growth, aggressiveness, drug resistance malignancies such glioblastoma, breast cancer, hepatocellular carcinoma. These fascinating advances knowledge acetyl-CoA during carcinogenesis normal physiology have raised interest regarding its modulation malignancies. In this review, we provide overview regulation cancer relevance main pathways participates. We summarize role reprogramming stress cells, well medical application inhibitors targeting dysregulation therapeutic intervention cancers.

Language: Английский

Citations

22
Critical Roles of the Cysteine–Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System DOI Open Access
Junichi Fujii, Tsukasa Osaki,

Yuya Soma

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8044 - 8044

Published: April 28, 2023

γ-Glutamyl moiety that is attached to the cysteine (Cys) residue in glutathione (GSH) protects it from peptidase-mediated degradation. The sulfhydryl group of Cys represents most functions GSH, which include electron donation peroxidases, protection reactive proteins via glutaredoxin, and conjugation xenobiotics, whereas Cys-derived sulfur also a pivotal component some redox-responsive molecules. amount available tends restrict capacity GSH synthesis. In vitro systems, cystine major form extracellular milieu, specific transporter, xCT, essential for survival lines cells many primary cultivated as well. A reduction supply causes GPX4 be inhibited due insufficient synthesis, leads iron-dependent necrotic cell death, ferroptosis. Cells generally cannot take up without removal γ-glutamyl by transferase (GGT) on surface. Meanwhile, Cys–GSH axis essentially common certain types cells; primarily, neuronal contain unique metabolic system intercellular communication concerning peptides. After general description processes axis, we provide an overview discuss significance GSH-related compounds nervous system.

Language: Английский

Citations

17
LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill DOI Creative Commons
Jirui Lang, Li Li,

Yunyun Quan

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 11, 2023

Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism not elucidated clearly. In present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied investigate alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics utilized analyze potential metabolic pathway effect WSP. The pharmacodynamic data discovered that could ameliorate ankle swelling inflammatory cell infiltration, as well downregulate protein expression IL-1β, p-NF-κB p65, NLRP3 synovial membrane surrounding tissues ankles. LC-MS-based revealed there were 30 differential between sham-operated rats ones, mainly involved metabolism fructose mannose, primary bile acid biosynthesis, cholesterol metabolism. compared model group, upregulated 11 biomarkers downregulated 31 serum. KEGG enrichment analysis found 27 pathways contributed therapeutic action WSP, including linoleic metabolism, phenylalanine pantothenate CoA biosynthesis. comprehensive analysis-combined network pharmacology further regulatory against gout might be attributed metabolites, 7 pathways, 39 targets, 49 active ingredients conclusion, inflammation rats, its relevant modulation multiple such This study provided support for secondary development Chinese patent medicine.

Language: Английский

Citations

15
Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments DOI Open Access
Chiara Cavestro, Daria Diodato, Valeria Tiranti

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5951 - 5951

Published: March 21, 2023

Coenzyme A (CoA) is a vital and ubiquitous cofactor required in vast number of enzymatic reactions cellular processes. To date, four rare human inborn errors CoA biosynthesis have been described. These disorders distinct symptoms, although all stem from variants genes that encode enzymes involved the same metabolic process. The first last catalyzing biosynthetic pathway are associated with two neurological conditions, namely pantothenate kinase-associated neurodegeneration (PKAN) COASY protein-associated (CoPAN), which belong to heterogeneous group neurodegenerations brain iron accumulation (NBIA), while second third linked rapidly fatal dilated cardiomyopathy. There still limited information about pathogenesis these diseases, knowledge gaps need be resolved order develop potential therapeutic approaches. This review aims provide summary metabolism functions, comprehensive overview what currently known its biosynthesis, including available preclinical models, proposed pathomechanisms,

Language: Английский

Citations

14
Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease DOI Creative Commons

Wesley Harrell Brooks

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 98(3), P. 837 - 857

Published: March 12, 2024

A hypothesis of Alzheimer’s disease etiology is proposed describing how cellular stress induces excessive polyamine synthesis and recycling which can disrupt nucleoli. Polyamines are essential in nucleolar functions, such as RNA folding ribonucleoprotein assembly. Changes the pool anionic cationic polyamines acting counterions cause significant dynamics. Polyamine reduces S-adenosylmethionine which, at low levels, triggers tau phosphorylation. Also, acetyl-CoA needed for acetylcholine, disease. Extraordinary expansion and/or contraction epigenetic control peri-nucleolar chromatin, chromosome 14 with presenilin-1 gene; 21 amyloid precursor protein 17 19 APOE4 inactive X (Xi; aka “nucleolar satellite”) normally silent spermine synthase (polyamine synthesis) spermidine/spermine-N1-acetyltransferase recycling) alleles. Chromosomes 17, Xi have high concentrations Alu elements be transcribed by polymerase III if positioned nucleosomes displaced from elements. sudden flood transcripts competitively bind nucleolin usually bound to sequences structural RNAs that stabilize heterochromatic shell. This competition leads loss integrity leaking aggregation phosphorylated tau. The was developed key word searches (e.g., PubMed) using relevant terms Alzheimer’s, lupus, nucleolin) based on a systems biology approach exploring autoimmune tautology, gaining synergistic insights other diseases.

Language: Английский

Citations

5