Metabolic switch regulates lineage plasticity and induces synthetic lethality in triple-negative breast cancer
Cell Metab. 2024 Jan 2;36(1):193-208.e8. doi: 10.1016/j.cmet.2023.12.003.ABSTRACTMetabolic reprogramming is key for cancer development, yet the mechanism that sustains triple-negative breast cancer (TNBC) cell growth despite deficient pyruvate kinase M2 (PKM2) and tumor glycolysis remains to be determined. Here, we find that deficiency in tumor glycolysis activates a metabolic switch from glycolysis to fatty acid β-oxidation (FAO) to fuel TNBC growth. We show that, in TNBC cells, PKM2 directly interacts with histone methyltransferase EZH2 to coordinately mediate epigenetic silencing of a carnitine transporter, SLC16A9. In...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Yingsheng Zhang Meng-Ju Wu Wan-Chi Lu Yi-Chuan Li Chun Ju Chang Jer-Yen Yang Source Type: research
Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution
Cell Metab. 2024 Jan 2;36(1):209-221.e6. doi: 10.1016/j.cmet.2023.12.005.ABSTRACTMetabolic status is crucial for stem cell functions; however, the metabolic heterogeneity of endogenous stem cells has never been directly assessed. Here, we develop a platform for high-throughput single-cell metabolomics (hi-scMet) of hematopoietic stem cells (HSCs). By combining flow cytometric isolation and nanoparticle-enhanced laser desorption/ionization mass spectrometry, we routinely detected >100 features from single cells. We mapped the single-cell metabolomes of all hematopoietic cell populations and HSC subpopulations with differ...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Jing Cao Qi Jason Yao Jiao Wu Xiaonan Chen Lin Huang Wanshan Liu Kun Qian Jing-Jing Wan Bo O Zhou Source Type: research
Mitochondrial-derived vesicles in metabolism, disease, and aging
Cell Metab. 2024 Jan 2;36(1):21-35. doi: 10.1016/j.cmet.2023.11.014.ABSTRACTMitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target organelles. Just recently, we gained significant insight i...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Tim K önig Heidi M McBride Source Type: research
The DEAD Box Protein Mrh4 Functions in the Assembly of the Mitochondrial Large Ribosomal Subunit
Cell Metab. 2024 Jan 2;36(1):222. doi: 10.1016/j.cmet.2023.11.016.NO ABSTRACTPMID:38171336 | DOI:10.1016/j.cmet.2023.11.016 (Source: Cell Metabolism)
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Dasmanthie De Silva Flavia Fontanesi Antoni Barrientos Source Type: research
H < sub > 2 < /sub > S serves as the immunoregulatory essence of apoptotic cell death
Cell Metab. 2024 Jan 2;36(1):3-5. doi: 10.1016/j.cmet.2023.12.006.ABSTRACTApoptosis supports tissue homeostasis and prevents immune disorders by removing damaged and functionally aberrant cells. Here, Ou et al. utilized genetic, pharmacological, and proteomic approaches focused on sulfur amino acid catabolism to discover that hydrogen sulfide (H2S) release during apoptosis suppresses Th17 cell differentiation, thus providing therapeutic targets for autoimmune diseases.PMID:38171337 | DOI:10.1016/j.cmet.2023.12.006 (Source: Cell Metabolism)
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Christopher Hine Andr ás K Ponti Mar ía Ángeles Cáliz-Molina Alejandro Mart ín-Montalvo Source Type: research
Show MERCI on mobile mitochondria
Cell Metab. 2024 Jan 2;36(1):5-7. doi: 10.1016/j.cmet.2023.12.017.ABSTRACTThere is emerging evidence that mitochondria can move between cells, particularly from immune cells into cancers. Recent work from Zhang et al. in Cancer Cell employs single-cell RNA- and mitochondrial DNA-sequencing in co-culture experiments and patient tumor samples to detect mitochondrial transfer. However, the mechanisms, scale, and implications remain uncertain.PMID:38171338 | DOI:10.1016/j.cmet.2023.12.017 (Source: Cell Metabolism)
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Jelle van den Ameele Patrick F Chinnery Source Type: research
What we talk about when we talk about spinal cord aging
Cell Metab. 2024 Jan 2;36(1):7-9. doi: 10.1016/j.cmet.2023.12.002.ABSTRACTSpinal cord-associated disorders are common in the elderly population; however, the mechanisms underlying spinal aging remain elusive. In a recent Nature paper, Sun et al. systemically analyzed aged spines in nonhuman primates and identified a new cluster of CHIT1-positive microglia that drives motor neuron senescence and subsequent spine aging.PMID:38171339 | DOI:10.1016/j.cmet.2023.12.002 (Source: Cell Metabolism)
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Xianhong Ji Jiajia Zhang Xiaoqiang Tang Hou-Zao Chen Source Type: research
Repression of latent NF- κB enhancers by PDX1 regulates β cell functional heterogeneity
Cell Metab. 2024 Jan 2;36(1):90-102.e7. doi: 10.1016/j.cmet.2023.11.018.ABSTRACTInteractions between lineage-determining and activity-dependent transcription factors determine single-cell identity and function within multicellular tissues through incompletely known mechanisms. By assembling a single-cell atlas of chromatin state within human islets, we identified β cell subtypes governed by either high or low activity of the lineage-determining factor pancreatic duodenal homeobox-1 (PDX1). β cells with reduced PDX1 activity displayed increased chromatin accessibility at latent nuclear factor κB (NF-κB) enhancers. Pdx1 ...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Benjamin J Weidemann Biliana Marcheva Mikoto Kobayashi Chiaki Omura Marsha V Newman Yumiko Kobayashi Nathan J Waldeck Mark Perelis Louise Lantier Owen P McGuinness Kathryn Moynihan Ramsey Roland W Stein Joseph Bass Source Type: research
TAMC-derived creatine sustains glioblastoma growth
Cell Metab. 2024 Jan 2;36(1):1-3. doi: 10.1016/j.cmet.2023.12.012.ABSTRACTTumor-associated myeloid cells (TAMCs) are the predominant immune population in glioblastoma (GBM), but the definite role of TAMCs in GBM tumorigenicity remains uncertain. In this issue of Cell Metabolism, Rashidi et al. identify a specific population of TAMCs surrounding hypoxic regions of GBM. These TAMCs provide creatine to nearby tumor cells to promote GBM progression.PMID:38171329 | DOI:10.1016/j.cmet.2023.12.012 (Source: Cell Metabolism)
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Huiwen Yan Pengcheng Bu Source Type: research
Glycine homeostasis requires reverse SHMT flux
Cell Metab. 2024 Jan 2;36(1):103-115.e4. doi: 10.1016/j.cmet.2023.12.001.ABSTRACTThe folate-dependent enzyme serine hydroxymethyltransferase (SHMT) reversibly converts serine into glycine and a tetrahydrofolate-bound one-carbon unit. Such one-carbon unit production plays a critical role in development, the immune system, and cancer. Using rodent models, here we show that the whole-body SHMT flux acts to net consume rather than produce glycine. Pharmacological inhibition of whole-body SHMT1/2 and genetic knockout of liver SHMT2 elevated circulating glycine levels up to eight-fold. Stable-isotope tracing revealed that the li...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Matthew J McBride Craig J Hunter Zhaoyue Zhang Tara TeSlaa Xincheng Xu Gregory S Ducker Joshua D Rabinowitz Source Type: research
Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD
Cell Metab. 2024 Jan 2;36(1):116-129.e7. doi: 10.1016/j.cmet.2023.12.013.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demons...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Alia Ghrayeb Alexandra C Finney Bella Agranovich Daniel Peled Sumit Kumar Anand M Peyton McKinney Mahasen Sarji Dongshan Yang Natan Weissman Shani Drucker Sara Isabel Fernandes Jonatan Fern ández-García Kyle Mahan Zaid Abassi Lin Tan Philip L Lorenzi Ja Source Type: research
Mitochondrial isocitrate dehydrogenase impedes CAR T cell function by restraining antioxidant metabolism and histone acetylation
Cell Metab. 2024 Jan 2;36(1):176-192.e10. doi: 10.1016/j.cmet.2023.12.010.ABSTRACTThe efficacy of chimeric antigen receptor (CAR) T cell therapy is hampered by relapse in hematologic malignancies and by hyporesponsiveness in solid tumors. Long-lived memory CAR T cells are critical for improving tumor clearance and long-term protection. However, during rapid ex vivo expansion or in vivo tumor eradication, metabolic shifts and inhibitory signals lead to terminal differentiation and exhaustion of CAR T cells. Through a mitochondria-related compound screening, we find that the FDA-approved isocitrate dehydrogenase 2 (IDH2) inh...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Xiaohui Si Mi Shao Xinyi Teng Yue Huang Ye Meng Longyuan Wu Jieping Wei Lianxuan Liu Tianning Gu Junzhe Song Ruirui Jing Xingyuan Zhai Xin Guo Delin Kong Xiujian Wang Bohan Cai Ying Shen Zhaoru Zhang Dongrui Wang Yongxian Hu Pengxu Qian Gang Xiao He Huang Source Type: research
Metabolic switch regulates lineage plasticity and induces synthetic lethality in triple-negative breast cancer
Cell Metab. 2024 Jan 2;36(1):193-208.e8. doi: 10.1016/j.cmet.2023.12.003.ABSTRACTMetabolic reprogramming is key for cancer development, yet the mechanism that sustains triple-negative breast cancer (TNBC) cell growth despite deficient pyruvate kinase M2 (PKM2) and tumor glycolysis remains to be determined. Here, we find that deficiency in tumor glycolysis activates a metabolic switch from glycolysis to fatty acid β-oxidation (FAO) to fuel TNBC growth. We show that, in TNBC cells, PKM2 directly interacts with histone methyltransferase EZH2 to coordinately mediate epigenetic silencing of a carnitine transporter, SLC16A9. In...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Yingsheng Zhang Meng-Ju Wu Wan-Chi Lu Yi-Chuan Li Chun Ju Chang Jer-Yen Yang Source Type: research
Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution
Cell Metab. 2024 Jan 2;36(1):209-221.e6. doi: 10.1016/j.cmet.2023.12.005.ABSTRACTMetabolic status is crucial for stem cell functions; however, the metabolic heterogeneity of endogenous stem cells has never been directly assessed. Here, we develop a platform for high-throughput single-cell metabolomics (hi-scMet) of hematopoietic stem cells (HSCs). By combining flow cytometric isolation and nanoparticle-enhanced laser desorption/ionization mass spectrometry, we routinely detected >100 features from single cells. We mapped the single-cell metabolomes of all hematopoietic cell populations and HSC subpopulations with differ...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Jing Cao Qi Jason Yao Jiao Wu Xiaonan Chen Lin Huang Wanshan Liu Kun Qian Jing-Jing Wan Bo O Zhou Source Type: research
Mitochondrial-derived vesicles in metabolism, disease, and aging
Cell Metab. 2024 Jan 2;36(1):21-35. doi: 10.1016/j.cmet.2023.11.014.ABSTRACTMitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target organelles. Just recently, we gained significant insight i...
Source: Cell Metabolism - January 3, 2024 Category: Cytology Authors: Tim K önig Heidi M McBride Source Type: research
