Glutamine availability regulates cDC subsets in tissue DOI
Graham P. Lobel, Nanumi Han, William A. Molina Arocho

et al.

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

Published: Sept. 21, 2024

Abstract Proliferating tumor cells take up glutamine for anabolic processes engendering deficiency in the microenvironment. How this might impact immune is not well understood. Using multiple mouse models of soft tissue sarcomas, antagonists, as genetic and pharmacological inhibition utilization, we found that number frequency conventional dendritic (cDC) dependent on microenvironmental levels. cDCs comprise two distinct subsets – cDC1 cDC2, with former subset playing a critical role antigen cross-presentation immunity. While both show dependence Glutamine, cDC1s are particularly sensitive. Notably, antagonism did reduce DC precursors but decreased proliferation survival cDC1s. Further studies suggest nutrient sensing mTOR signaling pathway process. Taken together, these findings uncover coopted by tumors to escape responses. One Sentence Summary Type 1 require maintain their non-lymphoid tissue. Significance Immune evasion key hallmark cancer; however, underlying pathways diverse, tumor-specific fully elucidated. Many avidly import support needs, creating glutamine-deficient microenvironment (TME). Herein, using depletion TME leads reduced type cell adaptive This work paradigm how metabolism can regulate anti-tumor responses will be foundational future efforts targeting cancer immunotherapy.

Language: Английский

The roles of mitochondria in global and local intracellular calcium signalling DOI
Benjamín Cartes-Saavedra, Arijita Ghosh, György Hajnóczky

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

5

Fluoride induces spermatocyte apoptosis by IP3R1/MCU-mediated mitochondrial calcium overload through MAMs DOI
Xin Guo, Linyuan Wang,

Jingyan Xuan

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 489, P. 137514 - 137514

Published: Feb. 5, 2025

Language: Английский

Citations

3

The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases DOI Creative Commons
Donato D’Angelo, Rosario Rizzuto

Biomolecules, Journal Year: 2023, Volume and Issue: 13(9), P. 1304 - 1304

Published: Aug. 25, 2023

Calcium (Ca2+) ions act as a second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by presence in inner mitochondrial membrane (IMM) uniporter (MCU) complex, macromolecular structure composed pore-forming and regulatory subunits. MtCa2+ plays crucial role oxidative metabolism death. A lot evidence demonstrates that dysregulation mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss molecular function MCU complex then focus our attention on human diseases which dysfunction has been shown.

Language: Английский

Citations

21

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance DOI Open Access
Neema Kumari,

Narasimha Pullaguri,

Subha Narayan Rath

et al.

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: March 15, 2024

Globally, cancer, as a major public health concern, poses severe threat to people’s well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance traditional novel chemotherapeutic drugs remains serious issue in clinical medicine. Chemoresistance often leads cancer recurrence, metastasis, increased mortality, accounting for 90% chemotherapy failures. Thus, it is important understand molecular mechanisms chemoresistance find therapeutic approaches treatment. Among several factors responsible chemoresistance, calcium (Ca2+) dysregulation plays significant role progression chemoresistance. Therefore, targeting this derailed Ca2+ signalling therapy has become an research area. Of note, signal its proteins are multifaceted potent tool by which cells achieve specific outcomes. Depending on cell survival needs, either upregulated or downregulated both chemosensitive chemoresistant cells. Consequently, appropriate treatment should be selected based dysregulation. This review discusses channels, pumps, exchangers. Furthermore, we have emphasised strategies. In conclusion, process. Methods such site-specific drug delivery, target-based drug-designing, two more simultaneously may explored; however, further studies essential validate blockers’ anti-cancer efficacy.

Language: Английский

Citations

6

Interaction and regulation of the mitochondrial proteome – in health and disease DOI Creative Commons
Johan Palmfeldt

Expert Review of Proteomics, Journal Year: 2025, Volume and Issue: 22(1), P. 19 - 33

Published: Jan. 2, 2025

Introduction Mitochondria contain multiple pathways including energy metabolism and several signaling synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases inherited metabolic disorders, complex common disorders like neurodegeneration, diabetes cancer, since they all to some degree have mitochondrial underpinnings.

Language: Английский

Citations

0

Crosstalk between Calcium and Reactive Oxygen Species Signaling in Cancer Revisited DOI

Trayambak Pathak,

J. Cory Benson, Priscilla W. Tang

et al.

Cell Calcium, Journal Year: 2025, Volume and Issue: unknown, P. 103014 - 103014

Published: March 1, 2025

Language: Английский

Citations

0

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis DOI

Lakra Promila,

Kabita Sarkar,

Shivika Guleria

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0

Mitochondrial Ca2+ controls pancreatic cancer growth and metastasis by regulating epithelial cell plasticity DOI Creative Commons
Jillian Weissenrieder, Jessica Peura,

Usha Paudel

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115627 - 115627

Published: April 25, 2025

Language: Английский

Citations

0

Lactate-associated gene MCU promotes the proliferation, migration, and invasion of pancreatic ductal adenocarcinoma DOI Creative Commons
Yuhang Chen, Fenglin Zhang,

Suoyi Dai

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 21, 2025

Language: Английский

Citations

0

Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma DOI Creative Commons
Nicole M. Marsh, Melissa J. S. MacEwen,

Jane Chea

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(22)

Published: May 28, 2025

Metabolic adaptations are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating pathways and signaling. However, comprehensive analysis of uniporter-regulated has remained unexplored. Here, we investigate consequences loss gain function using knockout cells fibrolamellar carcinoma (FLC), which demonstrate to have elevated levels. We find that branched-chain amino acid (BCAA) catabolism the urea cycle pathways. Reduced boosts expression BCAA genes enzyme ornithine transcarbamylase. In contrast, high activity FLC suppresses their expression. This suppression is mediated transcription factor KLF15, master regulator liver metabolism. Thus, central FLC-associated changes, including hyperammonemia. Our study identifies an important adaptation through transcriptional regulation metabolism elucidates its importance ammonia

Language: Английский

Citations

0