Pub Date : 2025-01-17DOI: 10.1016/j.cmet.2024.12.014
Jingwei Ma, Shuai Tong, Jingxuan Xiao, Bo Huang
Metabolism influences the behavior of various immune cell types. In a recent Cancer Cell study, Qiu et al. revealed mannose metabolism as a prominent metabolic feature of tumor precursor exhausted T cells (Tpex) that is crucial for maintaining T cell stemness. Their work uncovers a novel metabolic mechanism that decouples T cell proliferation from differentiation, providing valuable insights into how metabolic modulation can be used to generate “better” T cells during the manufacturing process.
{"title":"Mannose: A game-changer for T cell immunotherapy","authors":"Jingwei Ma, Shuai Tong, Jingxuan Xiao, Bo Huang","doi":"10.1016/j.cmet.2024.12.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.12.014","url":null,"abstract":"Metabolism influences the behavior of various immune cell types. In a recent <em>Cancer Cell</em> study, Qiu et al. revealed mannose metabolism as a prominent metabolic feature of tumor precursor exhausted T cells (Tpex) that is crucial for maintaining T cell stemness. Their work uncovers a novel metabolic mechanism that decouples T cell proliferation from differentiation, providing valuable insights into how metabolic modulation can be used to generate “better” T cells during the manufacturing process.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"10 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1016/j.cmet.2024.11.013
Youkun Bi, Xinlong Qiao, Zhaokui Cai, Hailian Zhao, Rong Ye, Qun Liu, Lin Gao, Yingqi Liu, Bo Liang, Yixuan Liu, Yaning Zhang, Zhiguang Yang, Yanyun Wu, Huiwen Wang, Wei Jia, Changqing Zeng, Ce Jia, Hongjin Wu, Yuanchao Xue, Guangju Ji
Cellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro. In aging mice, hESC-Exos treatment remodeled the proliferative landscape of SnCs, leading to rejuvenation, as evidenced by extended lifespan, improved physical performance, and reduced aging markers. Ago2 Clip-seq analysis identified miR-302b enriched in hESC-Exos that specifically targeted the cell cycle inhibitors Cdkn1a and Ccng2. Furthermore, miR-302b treatment reversed the proliferative arrest of SnCs in vivo, resulting in rejuvenation without safety concerns over a 24-month observation period. These findings demonstrate that exosomal miR-302b has the potential to reverse cellular senescence, offering a promising approach to mitigate senescence-related pathologies and aging.
{"title":"Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells","authors":"Youkun Bi, Xinlong Qiao, Zhaokui Cai, Hailian Zhao, Rong Ye, Qun Liu, Lin Gao, Yingqi Liu, Bo Liang, Yixuan Liu, Yaning Zhang, Zhiguang Yang, Yanyun Wu, Huiwen Wang, Wei Jia, Changqing Zeng, Ce Jia, Hongjin Wu, Yuanchao Xue, Guangju Ji","doi":"10.1016/j.cmet.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.11.013","url":null,"abstract":"Cellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs <em>in vitro</em>. In aging mice, hESC-Exos treatment remodeled the proliferative landscape of SnCs, leading to rejuvenation, as evidenced by extended lifespan, improved physical performance, and reduced aging markers. Ago2 Clip-seq analysis identified miR-302b enriched in hESC-Exos that specifically targeted the cell cycle inhibitors <em>Cdkn1a</em> and <em>Ccng2</em>. Furthermore, miR-302b treatment reversed the proliferative arrest of SnCs <em>in vivo</em>, resulting in rejuvenation without safety concerns over a 24-month observation period. These findings demonstrate that exosomal miR-302b has the potential to reverse cellular senescence, offering a promising approach to mitigate senescence-related pathologies and aging.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"36 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.cmet.2024.11.014
Shihao Zhang, Zenghui Cui, Danni Zhang, Deyu Zhang, Ke Jin, Zemeng Li, Bo Li, Boyi Cong, Juan Liu, Lei Wang, Mingyue Wen, Xuetao Cao
Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype. Through a large-scale metabolites-hnRNPA2B1 interaction screen, we reveal that adenine directly binds and activates hnRNPA2B1 to mediate innate antibacterial response. Mechanistically, adenine directly recruits hnRNPA2B1 to Il1b enhancers, and hnRNPA2B1 increases Il1b enhancer chromatin accessibility through binding and recruiting nucleolin and fat mass and obesity-associated protein (FTO) to mediate Il1b enhancer DNA N6-methyladenosine (6mA) demethylation. Furthermore, bacterial infection elevates nuclear adenine at the early stage of infection, and in vivo adenine administration protects mice from death upon bacterial infection through the hnRNPA2B1-IL-1β circuit. Our findings offer new insights into metabolic-epigenetic crosstalk relevant to antibacterial innate immunity and indicate potential approaches for treating bacterial infections.
{"title":"Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity","authors":"Shihao Zhang, Zenghui Cui, Danni Zhang, Deyu Zhang, Ke Jin, Zemeng Li, Bo Li, Boyi Cong, Juan Liu, Lei Wang, Mingyue Wen, Xuetao Cao","doi":"10.1016/j.cmet.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.11.014","url":null,"abstract":"Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing <em>Il1b</em> transcription. Myeloid cell-specific <em>Hnrnpa2b1</em>-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype. Through a large-scale metabolites-hnRNPA2B1 interaction screen, we reveal that adenine directly binds and activates hnRNPA2B1 to mediate innate antibacterial response. Mechanistically, adenine directly recruits hnRNPA2B1 to <em>Il1b</em> enhancers, and hnRNPA2B1 increases <em>Il1b</em> enhancer chromatin accessibility through binding and recruiting nucleolin and fat mass and obesity-associated protein (FTO) to mediate <em>Il1b</em> enhancer DNA N<sup>6</sup>-methyladenosine (6mA) demethylation. Furthermore, bacterial infection elevates nuclear adenine at the early stage of infection, and <em>in vivo</em> adenine administration protects mice from death upon bacterial infection through the hnRNPA2B1-IL-1β circuit. Our findings offer new insights into metabolic-epigenetic crosstalk relevant to antibacterial innate immunity and indicate potential approaches for treating bacterial infections.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"36 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease.
{"title":"Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring","authors":"Na Yao, Kenichiro Kinouchi, Manami Katoh, Kousha Changizi Ashtiani, Sherif Abdelkarim, Hiroyuki Morimoto, Takuto Torimitsu, Takahide Kozuma, Akihide Iwahara, Shotaro Kosugi, Jin Komuro, Kyosuke Kato, Shun Tonomura, Toshifumi Nakamura, Arata Itoh, Shintaro Yamaguchi, Jun Yoshino, Junichiro Irie, Hisayuki Hashimoto, Shinsuke Yuasa, Hiroshi Itoh","doi":"10.1016/j.cmet.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.12.002","url":null,"abstract":"Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. <em>In utero</em> circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"30 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13DOI: 10.1016/j.cmet.2024.11.012
Yizeng Fan, Weichao Dan, Yuzhao Wang, Zhiqiang Ma, Yanlin Jian, Tianjie Liu, Mengxing Li, Zixi Wang, Yi Wei, Bo Liu, Peng Ding, Yuzeshi Lei, Chendong Guo, Jin Zeng, Xiaolong Yan, Wenyi Wei, Lei Li
Itaconate is a metabolite catalyzed by cis-aconitate decarboxylase (ACOD1), which is mainly produced by activated macrophages and secreted into the extracellular environment to exert complex bioactivity. In the tumor microenvironment, itaconate is concentrated and induces an immunosuppressive response. However, whether itaconate can be taken up by tumor cells and its mechanism of action remain largely unclear. Here, we identified solute carrier family 13 member 3 (SLC13A3) as a key protein transporting extracellular itaconate into cells, where it elevates programmed cell death ligand 1 (PD-L1) protein levels and decreases the expression of immunostimulatory molecules, thereby promoting tumor immune evasion. Mechanistically, itaconate alkylates the cysteine 272 residue on PD-L1, antagonizing PD-L1 ubiquitination and degradation. Consequently, SLC13A3 inhibition enhances the efficacy of anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) immunotherapy and improves the overall survival rate in syngeneic mouse tumor models. Collectively, our findings identified SLC13A3 as a key transporter of itaconate and revealed its immunomodulatory role, providing combinatorial strategies to overcome immunotherapy resistance in tumors.
{"title":"Itaconate transporter SLC13A3 confers immunotherapy resistance via alkylation-mediated stabilization of PD-L1","authors":"Yizeng Fan, Weichao Dan, Yuzhao Wang, Zhiqiang Ma, Yanlin Jian, Tianjie Liu, Mengxing Li, Zixi Wang, Yi Wei, Bo Liu, Peng Ding, Yuzeshi Lei, Chendong Guo, Jin Zeng, Xiaolong Yan, Wenyi Wei, Lei Li","doi":"10.1016/j.cmet.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.11.012","url":null,"abstract":"Itaconate is a metabolite catalyzed by <em>cis-</em>aconitate decarboxylase (ACOD1), which is mainly produced by activated macrophages and secreted into the extracellular environment to exert complex bioactivity. In the tumor microenvironment, itaconate is concentrated and induces an immunosuppressive response. However, whether itaconate can be taken up by tumor cells and its mechanism of action remain largely unclear. Here, we identified solute carrier family 13 member 3 (SLC13A3) as a key protein transporting extracellular itaconate into cells, where it elevates programmed cell death ligand 1 (PD-L1) protein levels and decreases the expression of immunostimulatory molecules, thereby promoting tumor immune evasion. Mechanistically, itaconate alkylates the cysteine 272 residue on PD-L1, antagonizing PD-L1 ubiquitination and degradation. Consequently, SLC13A3 inhibition enhances the efficacy of anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) immunotherapy and improves the overall survival rate in syngeneic mouse tumor models. Collectively, our findings identified SLC13A3 as a key transporter of itaconate and revealed its immunomodulatory role, providing combinatorial strategies to overcome immunotherapy resistance in tumors.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"9 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08DOI: 10.1016/j.cmet.2024.11.011
Chao Liang, Abhilash Padavannil, Shan Zhang, Sheryl Beh, David R.L. Robinson, Jana Meisterknecht, Alfredo Cabrera-Orefice, Timothy R. Koves, Chika Watanabe, Miyuki Watanabe, María Illescas, Radiance Lim, Jordan M. Johnson, Shuxun Ren, Ya-Jun Wu, Dennis Kappei, Anna Maria Ghelli, Katsuhiko Funai, Hitoshi Osaka, Deborah Muoio, Lena Ho
Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I2+III2, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the Uqcrc1DEL:E258-D260 contact site mutation leads to respiratory decompensation. Lastly, SC-XL formation promotes fatty acid oxidation (FAO) and protects against ischemic heart failure in mice. Our study uncovers an unexpected plasticity in the mammalian ETC, where structural adaptations mitigate intrinsic perturbations, and suggests that manipulating SC-XL formation is a potential therapeutic strategy for mitochondrial dysfunction.
{"title":"Formation of I2+III2 supercomplex rescues respiratory chain defects","authors":"Chao Liang, Abhilash Padavannil, Shan Zhang, Sheryl Beh, David R.L. Robinson, Jana Meisterknecht, Alfredo Cabrera-Orefice, Timothy R. Koves, Chika Watanabe, Miyuki Watanabe, María Illescas, Radiance Lim, Jordan M. Johnson, Shuxun Ren, Ya-Jun Wu, Dennis Kappei, Anna Maria Ghelli, Katsuhiko Funai, Hitoshi Osaka, Deborah Muoio, Lena Ho","doi":"10.1016/j.cmet.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.11.011","url":null,"abstract":"Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I<sub>2</sub>+III<sub>2</sub>, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the Uqcrc1<sup>DEL:E258-D260</sup> contact site mutation leads to respiratory decompensation. Lastly, SC-XL formation promotes fatty acid oxidation (FAO) and protects against ischemic heart failure in mice. Our study uncovers an unexpected plasticity in the mammalian ETC, where structural adaptations mitigate intrinsic perturbations, and suggests that manipulating SC-XL formation is a potential therapeutic strategy for mitochondrial dysfunction.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"31 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07DOI: 10.1016/j.cmet.2024.12.003
Susana C.B.R. Nakandakari, Andin E. Fosam, Rachel J. Perry
Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis.
{"title":"The other side of the incretin story: GIPR signaling in energy homeostasis","authors":"Susana C.B.R. Nakandakari, Andin E. Fosam, Rachel J. Perry","doi":"10.1016/j.cmet.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.12.003","url":null,"abstract":"Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"28 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07DOI: 10.1016/j.cmet.2024.12.006
Sijie Tan, Nora Kory
Mitochondria produce energy and building blocks essential for cell growth. How these competing processes are balanced and sustained during nutrient scarcity remains unclear. Ryu et al. uncover distinct mitochondrial subpopulations, one dedicated to ATP production and another to macromolecule synthesis, enabling cell growth and proliferation under nutrient-limiting conditions.
{"title":"Divide and conquer, mitochondrial edition: Subpopulations direct cellular energy and nutrient supply","authors":"Sijie Tan, Nora Kory","doi":"10.1016/j.cmet.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.12.006","url":null,"abstract":"Mitochondria produce energy and building blocks essential for cell growth. How these competing processes are balanced and sustained during nutrient scarcity remains unclear. Ryu et al. uncover distinct mitochondrial subpopulations, one dedicated to ATP production and another to macromolecule synthesis, enabling cell growth and proliferation under nutrient-limiting conditions.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"22 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07DOI: 10.1016/j.cmet.2024.12.001
Sean M. Hartig, Mark A. Herman
De novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.
{"title":"Advancing de novo lipogenesis: Genetic and metabolic insights","authors":"Sean M. Hartig, Mark A. Herman","doi":"10.1016/j.cmet.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.12.001","url":null,"abstract":"<em>De novo</em> lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"35 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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