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

и другие.

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

Опубликована: Сен. 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.

Язык: Английский

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

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Язык: Английский

Процитировано

5

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

Jingyan Xuan

и другие.

Journal of Hazardous Materials, Год журнала: 2025, Номер 489, С. 137514 - 137514

Опубликована: Фев. 5, 2025

Язык: Английский

Процитировано

3

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

Biomolecules, Год журнала: 2023, Номер 13(9), С. 1304 - 1304

Опубликована: Авг. 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.

Язык: Английский

Процитировано

21

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

Narasimha Pullaguri,

Subha Narayan Rath

и другие.

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Март 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.

Язык: Английский

Процитировано

6

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

Expert Review of Proteomics, Год журнала: 2025, Номер 22(1), С. 19 - 33

Опубликована: Янв. 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.

Язык: Английский

Процитировано

0

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

Trayambak Pathak,

J. Cory Benson, Priscilla W. Tang

и другие.

Cell Calcium, Год журнала: 2025, Номер unknown, С. 103014 - 103014

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

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

и другие.

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

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

Usha Paudel

и другие.

Cell Reports, Год журнала: 2025, Номер 44(5), С. 115627 - 115627

Опубликована: Апрель 25, 2025

Язык: Английский

Процитировано

0

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

Suoyi Dai

и другие.

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Май 21, 2025

Язык: Английский

Процитировано

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

и другие.

Science Advances, Год журнала: 2025, Номер 11(22)

Опубликована: Май 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

Язык: Английский

Процитировано

0