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| 1 | Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress显示文摘AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity. | Yue Zong Chen-Song Zhang Mengqi Li Wen Wang Zhichao Wang Simon A. Hawley Teng Ma Jin-Wei Feng Xiao Tian Qu Qi Yu-Qing Wu Cixiong Zhang Zhiyun Ye Shu-Yong Lin Hai-Long Piao D. Grahame Hardie Sheng-Cai Lin | 2019 | Cell Research2019，29，6： | 8 |
| 2 | The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation显示文摘由葡萄糖 transporter GLUT4 的刺激胰岛素的葡萄糖举起在整个身体的葡萄糖动态平衡起一个中央作用,哪个导致类型 2 糖尿病的 dysregulation。然而,调整刺激胰岛素的葡萄糖举起的分子的部件和机制仍然保持大部分不清楚。这里,我们证明 Axin 与 ADP-ribosylase tankyrase 交往 2 (TNKS2 ) 并且 kinesin 马达蛋白质 KIF3A,响应胰岛素形成为 GLUT4 translocation 关键的第三的建筑群。特定到血浆膜的复杂稀释刺激胰岛素的 GLUT4 translocation 的单个部件击倒。重要地, TNKS2 −/− 老鼠展出减少的胰岛素敏感和更高的血葡萄糖层次什么时候在 fasting 以后的 re-fed。机械学地,我们证明当胰岛素不在时, Axin, TNKS 和 KIF3A 与 trans-Golgi 网络上的 GLUT4 是 co 局部性的。胰岛素处理压制 TNKS 的 ADP-ribosylase 活动,导致在自动数据处理 ribosylation 和 ubiquitination 的减小 Axin 和 TNKS,和建筑群的并发的稳定。Akt 的抑制,胰岛素发信号的主要受动器 kinase,废除调停胰岛素的复杂稳定。我们因此阐明了直接在刺激胰岛素的 GLUT4 translocation 与马达蛋白质 kinesin 被联系的新蛋白质建筑群。 | Hui-Ling Guo Cixiong Zhang Qi Liu Qinxi Li Guili Lian Di Wu Xuebin Li Wei Zhang Yuemao Shen Zhiyun Ye Slau-Yong Lin Sheng-Cai Lin | 2012 | Cell Research2012，22，8： | 4 |
| 3 | Glutaminase GLS1 senses glutamine availability in a non-enzymatic manner triggering mitochondrial fusion显示文摘 | Wei-Feng Cai Cixiong Zhang Yu-Qing Wu Gui Zhuang Zhiyun Ye Chen-Song Zhang Sheng-Cai Lin | 2018 | Cell Research2018，28，8： | 4 |
| 4 | Identification of serum metabolites enhancing inflammatory responses in COVID-19显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is characterized by a strong production of inflammatory cytokines such as TNF and IL-6,which underlie the severity of the disease.However,the molecular mechanisms responsible for such a strong immune response remains unclear.Here,utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages,we identified that 611 metabolites(of 1,039)were significantly altered in COVID-19 patients.Among them,two metabolites,agmatine and putrescine,were prominently elevated in the serum of patients;and 2-quinolinecarboxylate was changed in a biphasic manner,elevated during early COVID-19 infection but levelled off.When tested in mouse embryonic fibroblasts(MEFs)and macrophages,these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production.Importantly,these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice,but not in the mice lacking NF-κB.Intriguingly,these metabolites have little effects on the activation of interferon regulatory factors(IRFs)for the production of type I interferons(IFNs)for antiviral defenses.These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses,exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons.Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients. | Chen-Song Zhang Bingchang Zhang Mengqi Li Xiaoyan Wei Kai Gong Zhiyong Li Xiangyang Yao Jianfeng Wu Cixiong Zhang Mingxia Zhu Lei Zhang Xiufeng Sun Yi-Hong Zhan Zhengye Jiang Wenpeng Zhao Wei Zhong Xinguo Zhuang Dawang Zhou Hai-Long Piao Sheng-Cai Lin Zhanxiang Wang | 2022 | Science China(Life Sciences)2022，65，10： | 1 |
| 5 | AIDA通过内质网相关的蛋白质降解途径选择性下调脂肪合成途径的代谢酶从而减缓肠道脂肪吸收并防止肥胖发生显示文摘文章简介肠道对膳食脂肪吸收的效率是个人是否易患肥胖的主要决定因素之一。然而,目前人们还不清楚脂肪吸收是如何受调控并导致肥胖的。本研究表明,抑制内质网相关的蛋白质降解途径会提高甘油三酯合成途径的数个代谢酶的水平,并促进小肠对脂肪的吸收。 | 罗辉 姜鸣 Guili Lian Qing Liu Meng Shi Terytty Yang Li Lintao Song Jing Ye Ying He Luming Yao Cixiong Zhang Zhi-Zhong Lin Chen-Song Zhang Tong-Jin Zhao Wei-Ping Jia Peng Li 林舒勇 林圣彩 | 2019 | 科学新闻2019，0，2： | 1 |
| 6 | ULK1/2所构成的信号节点除控制细胞自噬外还控制葡萄糖代谢通路显示文摘在细胞感受到环境中营养物质和生长因子的提供量发生改变后,代谢通路的重编程对于维持此时胞内的稳态是非常重要的过程。ULK1和ULK2是传递外界应激信号至自噬发生的重要整合因子。 | Terytty Yang Li Yu Sun Yu Liang Qing Liu Yuzhe Shi Chen-Song Zhang Cixiong Zhang Lintao Song Pu Zhang Xianzhong Zhang Xiaotong Li Tao Chen Hui-Ying Huang Xiadi He Yi Wang Yu-Qing Wu Shaoxuan Chen Ming Jiang Canhe Chen Changchuan Xie James Y.Yang Yan Lin Shimin Zhao Zhiyun Ye Shu-Yong Lin Daniel Tsun-yee Chiu 林圣彩 | 2017 | 科学新闻2017，19，4： | 0 |
| 7 | 阳离子通道TRPV在醛缩酶和AMPK感知葡萄糖过程中起必须的作用显示文摘文章简介在激活AMPK的溶酶体途径感应葡萄糖供给下降的过程中,果糖-1,6-二磷酸醛缩酶(aldolase)起关键作用。然而,醛缩酶是如何把其与果糖-1,6-二磷酸结合的减少的信息传导引起AMPK活化的机制还尚未清楚。 | Mengqi Li Chen-Song Zhang Yue Zong Jin-Wei Feng Teng Ma Meiqin Hu Zhizhong Lin Xiaotong Li Changchuan Xie Yaying Wu Dong Jiang Ying Li Cixiong Zhang Xiao Tian Wen Wang Yanyan Yang Jie Chen Jiwen Cui Yu-Qing Wu Xin Chen Qing-Feng Liu Jianfeng Wu Shu-Yong Lin Zhiyun Ye Ying Liu Hai-Long Piao Li Yu Zhuan Zhou Xiao-Song Xie D.Grahame Hardie 林圣彩 | 2020 | 科学新闻2020，，2： | 0 |
| 8 | Aldolase is a sensor for both low and high glucose,linking to AMPK and mTORC1显示文摘Dear Editor,As well as glucose being the major carbon nutrient for most cells,its availability also acts as a gate-keeper exerting a switch between anabolic and catabolic metabolism,with the protein kinases mTORC1 and AMP-activated protein kinase(AMPK)being the two master controllers.1 In low glucose,AMPK is activated and phosphorylates a wide range of downstream targets to maintain energy homeostasis,by switching on catabolic pathways while switching off ATP-consuming processes.1 In high glucose,mTORC1 is activated and shifts the metabolic program of the cell towards anabolic metabolism.1 It is already known that low glucose,and hence low levels of the glycolytic intermediate fructose-1,6-bisphosphate(FBP),can be sensed by aldolase to trigger AMPK activation via the lysosomal pathway.2,3 This occurs independently of increases in AMP and ADP,the classical activators of AMPK.2 Although it is clear that mTORC1 is also regulated by glucose availability at multiple levels,the underlying mechanisms have not been fully elucidated. | Mengqi Li Chen-Song Zhang Jin-Wei Feng Xiaoyan Wei Cixiong Zhang Changchuan Xie Yaying Wu Simon A.Hawley Abdelmadjid Atrih Douglas J.Lamont Zhichao Wang Hai-Long Piao D.Grahame Hardie Sheng-Cai Lin | 2021 | Cell Research2021，31，4： | 0 |
| 9 | Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate显示文摘Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals,controlling metabolic states beyond energy metabolism.However,whether glycolytic metabolites also play a role in controlling cell fate remains unexplored.Here,we find that low levels of glycolytic metabolite 3-phosphoglycerate(3-PGA)can switch phosphoglycerate dehydrogenase(PHGDH)from cataplerosis serine synthesis to pro-apoptotic activation of p53.PHGDH is a p53-binding protein,and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2,both of which are also p53-binding proteins.This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis.Furthermore,we show that PHGDH mutants(R135W and V261M)that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions,while the mutants(T57A and T78A)unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma(HCC)cells,even in the presence of high glucose.In vivo,PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC,whereas PHGDH-R135W prevents apoptosis and promotes HCC growth,and knockout of Trp53 abolishes these effects above.Importantly,caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH.Together,these results unveil a mechanism by which glucose availability autonomously controls p53 activity,providing a new paradigm of cell fate control by metabolic substrate availability. | Yu-Qing Wu Chen-Song Zhang Jinye Xiong Dong-Qi Cai Chen-Zhe Wang Yu Wang Yan-Hui Liu Yu Wang Yiming Li Jian Wu Jianfeng Wu Bin Lan Xuefeng Wang Siwei Chen Xianglei Cao Xiaoyan Wei Hui-Hui Hu Huiling Guo Yaxin Yu Abdul Ghafoor Changchuan Xie Yaying Wu Zheni Xu Cixiong Zhang Mingxia Zhu Xi Huang Xiufeng Sun Shu-Yong Lin Hai-Long Piao Jianyin Zhou Sheng-Cai Lin | 2023 | Cell Research2023，33，11： | 0 |
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