From Molecular Subgroups to Molecular Targeted Therapy in Rheumatoid Arthritis: A Bioinformatics Approach DOI Creative Commons
Yangyang Xu, Zhenyu Yang, Tengyan Wang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(16), P. e35774 - e35774

Published: Aug. 1, 2024

Rheumatoid Arthritis (RA) is a heterogeneous autoimmune disease with multiple unidentified pathogenic factors. The inconsistency between molecular subgroups poses challenges for early diagnosis and personalized treatment strategies. In this study, we aimed to accurately distinguish RA patients at the transcriptome level using bioinformatics methods.

Language: Английский

Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation DOI Open Access
Tsung‐Hsien Chen, Hsiang‐Chen Wang, Chia-Jung Chang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1314 - 1314

Published: Jan. 21, 2024

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from substrates oxygen produce adenosine triphosphate. also regulate proliferation, metastasis, and deterioration. The flow in mitochondrial respiratory chain generates reactive species (ROS), which harmful cells at high levels. stress caused by ROS accumulation has been associated with an increased risk cancer, cardiovascular liver diseases. Glutathione (GSH) is abundant cellular antioxidant that primarily synthesized cytoplasm delivered mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within A long-term imbalance ratio mGSH can cause dysfunction, apoptosis, necroptosis, ferroptosis, may lead disease. This study aimed review physiological functions, anabolism, variations organ tissue accumulation, delivery GSH mitochondria relationships between levels, GSH/GSH disulfide (GSSG) ratio, programmed death, ferroptosis. We discuss diseases deficiency related therapeutics.

Language: Английский

Citations

54
Why cells need iron: a compendium of iron utilisation DOI Creative Commons
Megan R. Teh, Andrew E. Armitage, Hal Drakesmith

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron utilised in a variety ways by hundreds different proteins. Here, we review links between molecular activities regulated the pathophysiological effects deficiency. We identify specific enzyme groups, biochemical pathways, cellular functions, cell lineages that are particularly dependent. provide examples how deprivation influences multiple key systems tissues, including immunity, hormone synthesis, cholesterol metabolism. propose greater mechanistic understanding physiological processes may lead new therapeutic opportunities across range diseases.

Language: Английский

Citations

16
Solute carriers: The gatekeepers of metabolism DOI
Artem Khan, Yuyang Liu, Mark Gad

et al.

Cell, Journal Year: 2025, Volume and Issue: 188(4), P. 869 - 884

Published: Feb. 1, 2025

Language: Английский

Citations

1
Transcriptomic profile of premature ovarian insufficiency with RNA-sequencing DOI Creative Commons

Jiaman Wu,

Shiyu Feng,

Yan Luo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 9, 2024

Introduction This study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression. Methods A total sixty-one women, comprising 31 individuals with POI group and 30 healthy women control (HC group), aged between 24 40 years, were recruited for this study. The profiles peripheral blood samples from all subjects analyzed using RNA-sequencing. Results results revealed 39 differentially expressed genes compared controls, 10 upregulated 29 downregulated genes. Correlation analysis highlighted relationship expression SLC25A39, CNIH3, PDZK1IP1 hormone levels. Additionally, an effective classification model was developed PDZK1IP1, SHISA4, LOC389834. Functional enrichment demonstrated involvement these “haptoglobin-hemoglobin complex,” while KEGG pathway indicated their participation “Proteoglycans cancer” pathway. Conclusion identified could play a crucial role characterizing genetic foundation POI, potentially serving as valuable biomarkers enhancing disease accuracy.

Language: Английский

Citations

5
Immunometabolism of ferroptosis in the tumor microenvironment DOI Creative Commons
Gian Luca Lupica-Tondo, Emily N. Arner, Denis A. Mogilenko

et al.

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

Published: Aug. 12, 2024

Ferroptosis is an iron-dependent form of cell death that results from excess lipid peroxidation in cellular membranes. Within the last decade, physiological and pathological roles for ferroptosis have been uncovered autoimmune diseases, inflammatory conditions, infection, cancer biology. Excitingly, metabolism may be targeted to induce by cancers are resistant other forms death. sensitivity regulated oxidative stress, metabolism, iron which all influenced tumor microenvironment (TME). Whereas some types shown adapt these stressors, it not clear how immune cells regulate their sensitivities ferroptosis. In this review, we discuss mechanisms different subsets, influences infiltrate TME, interactions can determine epithelial-to-mesenchymal transition (EMT) metastasis. While much focus has placed on inducing cells, important considerations ferroptosis-modulating strategies impact anti-tumor immunity. From perspective, also promising immunotherapies field challenges associated with targeting specific populations.

Language: Английский

Citations

5
Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol DOI Creative Commons
Joseph J. Braymer, Oliver Stehling,

Martin Stümpfig

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(21)

Published: May 14, 2024

The biogenesis of iron–sulfur (Fe/S) proteins entails the synthesis and trafficking Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, multiple steps are accomplished complex protein machineries in both mitochondria cytosol. underlying biochemical pathways have been elucidated over past decades, yet mechanisms cytosolic [2Fe-2S] assembly remained ill-defined. Similarly, precise site glutathione (GSH) requirement nuclear is unclear, as molecular role GSH-dependent monothiol glutaredoxins (cGrxs). Here, we investigated these questions human yeast cells various vivo approaches. cluster apoproteins required mitochondrial ISC machinery, transporter Atm1/ABCB7 GSH, occurred independently CIA system cGrxs. This mechanism was strikingly different from ISC-, Atm1/ABCB7-, GSH-, CIA-dependent cytosolic–nuclear [4Fe-4S] proteins. One notable exception to this maturation pathway defined here Apd1 which used via binding targeting through its C-terminal tryptophan. cGrxs, although attributed chaperones or proteins, were not essential for delivering clusters either components Finally, most critical GSH assigned Atm1-dependent export, i.e. a step before cGrxs function. Our findings extend general model eukaryotic adding requirements maturation.

Language: Английский

Citations

4
SLC25A38 is required for mitochondrial pyridoxal 5’-phosphate (PLP) accumulation DOI Creative Commons
Izabella A. Pena, Ju Shi, Sarah Chang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important amino acid metabolism, one-carbon polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third all mammalian 5'-phosphate-dependent are localized in mitochondria; however, molecular machinery involved regulation mitochondrial 5'-phosphate levels mammals remains unknown. In this study, we used genome-wide CRISPR interference screen erythroleukemia cells organellar metabolomics to identify inner membrane protein SLC25A38 regulator 5'-phosphate. Loss causes depletion mitochondrial, but not cellular, impairs cellular proliferation under both physiological low B6 conditions. Metabolic changes associated with loss suggest impaired enzymatic reactions, including serine glycine conversion catalyzed by hydroxymethyltransferase-2 well ornithine aminotransferase. The defect SLC25A38-null K562 media can be explained hydroxymethyltransferase-2-dependent production units downstream de novo nucleotide synthesis. Our work points role accumulation provides insights into pathology congenital sideroblastic anemia. Pyridoxal (PLP, B6) is crucial various metabolic processes. Here, authors identified key PLP using CRISPRi metabolomics,

Language: Английский

Citations

0
Targeting mitochondria-regulated ferroptosis: A new frontier in Parkinson’s Disease therapy DOI Creative Commons
Wenjun Wang,

Elizabeth Rosalind Thomas,

Rui Xiao

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110439 - 110439

Published: March 1, 2025

Language: Английский

Citations

0
SLC25A39 links mitochondrial GSH sensing with iron metabolism DOI Creative Commons
Xiong Chen, Boyi Gan

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 616 - 618

Published: Feb. 1, 2024

Language: Английский

Citations

3
Pulling back the mitochondria’s iron curtain DOI Creative Commons

Shani Ben Zichri- David,

Liraz Shkuri,

Tslil Ast

et al.

npj Metabolic Health and Disease, Journal Year: 2025, Volume and Issue: 3(1)

Published: March 4, 2025

Language: Английский

Citations

0