MetaboList – June 2022


Nutrient sensing – mTOR


Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine – Andrew L. Cangelosi, Anna M. Puszynska, Justin M. Roberts, Andrea Armani, Thao P. Nguyen, Jessica B. Spinelli, Tenzin Kunchok, Brianna Wang, Sze Ham Chan, Caroline A. Lewis, William C. Comb, George W. Bell, Aharon Helman, David M. Sabatini. https://www.science.org/doi/abs/10.1126/science.abi9547

Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1 – Gwen R. Buel, Huy Q. Dang, John M. Asara, John Blenis, Anders P. Mutvei. https://www.jbc.org/article/S0021-9258(22)00470-7/fulltext

Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation – Hongrui Xiang, Yuexiao Tao, Zhenyan Jiang, Xian Huang, Huizi Wang, Wei Cao, Jia Li, Rui Ding, Mingyi Shen, Ru Feng, Linsen Li, Chenyang Guan, Jiamin Liu, Jun Ni, Lei Chen, Zhengting Wang, Youqiong Ye, Qing Zhong, Junling Liu, Qiang Zou, Xuefeng Wu. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00725-2


Nutrient sensing – ISR


A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression – Ioannis I. Verginadis, Harris Avgousti, James Monslow, Giorgos Skoufos, Frank Chinga, Kyle Kim, Nektaria Maria Leli, Ilias V. Karagounis, Brett I. Bell, Anastasia Velalopoulou, Carlo Salas Salinas, Victoria S. Wu, Yang Li, Jiangbin Ye, David A. Scott, Andrei L. Osterman, Arjun Sengupta, Aalim Weljie, Menggui Huang, Duo Zhang, Yi Fan, Enrico Radaelli, John W. Tobias, Florian Rambow, Panagiotis Karras, Jean-Christophe Marine, Xiaowei Xu, Artemis G. Hatzigeorgiou, Sandra Ryeom, J. Alan Diehl, Serge Y. Fuchs, Ellen Puré and Constantinos Koumenis. https://www.nature.com/articles/s41556-022-00918-8

Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific – Jonsson WO, Mirek ET, Wek RC, Anthony TG. https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202200204RR

Cellular responses to halofuginone reveal a vulnerability of the GCN2 branch of the integrated stress response – Aleksandra P Pitera, Maria Szaruga, Sew-Yeu Peak-Chew, Steven W Wingett, Anne Bertolotti. https://www.embopress.org/doi/full/10.15252/embj.2021109985


Nutrient sensing: AMPK


A novel AMPK activator shows therapeutic potential in hepatocellular carcinoma by suppressing HIF1α‐mediated aerobic glycolysis – Hsing-I Tseng, Yi-Siang Zeng, Ying-Chung Jimmy Lin, Jui-Wen Huang, Chih-Lung Lin, Meng-Hsuan Lee, Fan-Wei Yang, Te-Ping Fang, Ai-Chung Mar, Jung-Chen Su. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13211

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator – Ashley J. Ovens, Yi Sing Gee, Naomi X.Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung; Kevin R.W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf. https://portlandpress.com/biochemj/article/479/11/1181/231304

Translation initiation factor eIF3a regulates glucose metabolism and cell proliferation via promoting small GTPase Rheb synthesis and AMPK activation – Shijie Ma, Zizheng Dong, Yanfei Huang, Jing-Yuan Liu, Jian-Ting Zhang. https://www.jbc.org/article/S0021-9258(22)00484-7/fulltext


Nutrient sensing – miscellaneous


The polyol pathway is an evolutionarily conserved system for sensing glucose uptake – Hiroko Sano, Akira Nakamura, Mariko Yamane, Hitoshi Niwa, Takashi Nishimura, Kimi Araki, Kazumasa Takemoto, Kei-ichiro Ishiguro, Hiroki Aoki, Yuzuru Kato, Masayasu Kojima. https://www.nature.com/articles/s42255-022-00568-y

Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth – Chunming Cheng, Feng Geng, Zoe Li, Yaogang Zhong, Huabao Wang, Xiang Cheng, Yue Zhao, Xiaokui Mo, Craig Horbinski, Wenrui Duan, Arnab Chakravarti, Xiaolin Cheng and Deliang Guo. https://www.nature.com/articles/s42255-022-00568-y

Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors – Melvin Pan, Christiane Zorbas and Tsuyoshi Osawa. https://www.nature.com/articles/s41467-022-31418-w

A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth – Yu Ting Ong, Jorge Andrade, Max Armbruster, Chenyue Shi, Marco Castro, Ana S. H. Costa, Toshiya Sugino, Guy Eelen, Barbara Zimmermann, Kerstin Wilhelm, Joseph Lim, Shuichi Watanabe, Stefan Guenther, Andre Schneider, Francesca Zanconato, Manuel Kaulich, Duojia Pan, Thomas Braun, Holger Gerhardt, Alejo Efeyan, Peter Carmeliet, Stefano Piccolo, Ana Rita Grosso and Michael Potente. https://www.nature.com/articles/s42255-022-00584-y


Hypoxia


Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia – Javier Garcia-Bermudez, Michael A. Badgley, Sheela Prasad, Lou Baudrier, Yuyang Liu, Konnor La, Mariluz Soula, Robert T. Williams, Norihiro Yamaguchi, Rosa F. Hwang, Laura J. Taylor, Elisa de Stanchina, Bety Rostandy, Hanan Alwaseem, Henrik Molina, Dafna Bar-Sagi and Kıvanç Birsoy. https://www.nature.com/articles/s42255-022-00583-z

Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome – Shuijie Li, Wenyu Li, Juan Yuan, Petra Bullova, Jieyu Wu, Xuepei Zhang, Yong Liu, Monika Plescher, Javier Rodriguez, Oscar C. Bedoya-Reina, Paulo R. Jannig, Paula Valente-Silva, Meng Yu, Marie Arsenian Henriksson, Roman A. Zubarev, Anna Smed-Sörensen, Carolyn K. Suzuki, Jorge L. Ruas, Johan Holmberg, Catharina Larsson, C. Christofer Juhlin, Alex von Kriegsheim, Yihai Cao and Susanne Schlisio. https://www.nature.com/articles/s42255-022-00593-x

Hypoxia-inducible factor-1α and poly [ADP ribose] polymerase 1 cooperatively regulate Notch3 expression under hypoxia via a non-canonical mechanism – Hideaki Nakamura, Hiroki Sekine, Hiroyuki Kato, Hisao Masai, Katarina Gradin, Lorenz Poellinger. https://www.jbc.org/article/S0021-9258(22)00579-8/fulltext


Glucose metabolism


G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment – Shree Bose, Qiang Huang, Yunhan Ma, Lihua Wang, Grecia O. Rivera, Yunxin Ouyang, Regina Whitaker, Rebecca A. Gibson, Christopher D. Kontos, Andrew Berchuck, Rebecca A. Previs, Xiling Shen. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00801-4

A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect – Xuejun Wen; Changrong Shi;, Xinying Zeng, Liang Zhao, Lanlin Yao, Zhida Liu, Lixia Feng, Deliang Zhang, Jinxiong Huang, Yesen Li, Qin Lin, Haojun Chen, Rongqiang Zhuang, Xiaoyuan Chen,  Xianzhong Zhang, Zhide Guo. https://aacrjournals.org/clincancerres/article-abstract/28/13/2923/704989

The metabolic enzyme hexokinase 2 localizes to the nucleus in AML and normal haematopoietic stem and progenitor cells to maintain stemness – Geethu Emily Thomas, Grace Egan, Laura García-Prat, Aaron Botham, Veronique Voisin, Parasvi S. Patel, Fieke W. Hoff, Jordan Chin, Boaz Nachmias, Kerstin B. Kaufmann, Dilshad H. Khan, Rose Hurren, Xiaoming Wang, Marcela Gronda, Neil MacLean, Cristiana O’Brien, Rashim P. Singh, Courtney L. Jones, Shane M. Harding, Brian Raught, Andrea Arruda, Mark D. Minden, Gary D. Bader, Razq Hakem, Steve Kornblau, John E. Dick and Aaron D. Schimmer. https://www.nature.com/articles/s41556-022-00925-9


Amino acid metabolism


Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix – Emily J. Kay, Karla Paterson, Carla Riero-Domingo, David Sumpton, J. Henry M. Däbritz, Saverio Tardito, Claudia Boldrini, Juan R. Hernandez-Fernaud, Dimitris Athineos, Sandeep Dhayade, Ekaterina Stepanova, Enio Gjerga, Lisa J. Neilson, Sergio Lilla, Ann Hedley, Grigorios Koulouras, Grace McGregor, Craig Jamieson, Radia Marie Johnson, Morag Park, Kristina Kirschner, Crispin Miller, Jurre J. Kamphorst, Fabricio Loayza-Puch, Julio Saez-Rodriguez, Massimiliano Mazzone, Karen Blyth, Michele Zagnoni and Sara Zanivan. https://www.nature.com/articles/s42255-022-00582-0

Mitochondrial Calcium Uniporter Drives Metastasis and Confers a Targetable Cystine Dependency in Pancreatic Cancer – Xiuchao Wang, Yunzhan Li, Zekun Li, Shengchen Lin, Hongwei Wang, Jianwei Sun, Chungen Lan, Liangliang Wu, Dongxiao Sun, Chongbiao Huang, Pankaj K. Singh, Nadine Hempel, Mohamed Trebak, Gina M. DeNicola, Jihui Hao, Shengyu Yang. https://aacrjournals.org/cancerres/article-abstract/82/12/2254/699357

Characterizing unexpected interactions of a glutamine transporter inhibitor with members of the SLC1A transporter family – Natasha Freidman, Chelsea Briot, Renae Ryan. https://www.jbc.org/article/S0021-9258(22)00620-2

mTORC1-independent translation control in mammalian cells by methionine adenosyltransferase 2A and S-adenosylmethionine – Mahabub Alam, Hiroki Shima, Yoshitaka Matsuo, Nguyen Chi Long, Mitsuyo Matsumoto, Yusho Ishii, Nichika Sato, Takato Sugiyama, Risa Nobuta, Satoshi Hashimoto, Liang Liu, Mika K. Kaneko, Yukinari Kato, Toshifumi Inada, Kazuhiko Igarashi. https://www.jbc.org/article/S0021-9258(22)00525-7/fulltext

Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML – Chang Liu, Waiyi Zou, Danian Nie, Shuyi Li, Chen Duan, Min Zhou, Peilong Lai, Shengyong Yang, Sen Ji, Yangqiu Li, Mei Mei, Shilai Bao, Yanli Jin, Jingxuan Pan. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00131-0

Asparagine synthetase regulates lung-cancer metastasis by stabilizing the β-catenin complex and modulating mitochondrial response – Dong-Jing Cai, Zi-Yu Zhang, Yue Bu, Li Li, Yue-Zhen Deng, Lun-Quan Sun, Cheng-Ping Hu and Min Li. https://www.nature.com/articles/s41419-022-05015-0


Lipid metabolism


Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited – Zhaoqi Li, Brian W. Ji, Purushottam D. Dixit, Konstantine Tchourine, Evan C. Lien, Aaron M. Hosios, Keene L. Abbott, Justine C. Rutter, Anna M. Westermark, Elizabeth F. Gorodetsky, Lucas B. Sullivan, Matthew G. Vander Heiden and Dennis Vitkup. https://www.nature.com/articles/s42255-022-00588-8

The short-chain fatty acid acetate modulates epithelial-to-mesenchymal transition – Junfang Lyu, Mehdi Pirooznia, Yuesheng Li, and Jianhua Xiong. https://www.molbiolcell.org/doi/10.1091/mbc.E22-02-0066?ai=s5&ui=2oy6&af=T

Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation – Yutang Huang, Yan Du, Yujie Zheng, Chunjie Wen, Hecun Zou, Jiafeng Huang, Honghao Zhou, Hongbo Zhao and Lanxiang Wu. https://www.nature.com/articles/s41419-022-05014-1

MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma – Ling Tao, Mahmoud A. Mohammad and Eveline Barbieri. https://www.nature.com/articles/s41467-022-31331-2


Mitochondria and iron


NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins – Naiara Santana-Codina, Maria Quiles del Rey, Kevin S. Kapner, Huan Zhang, Ajami Gikandi, Callum Malcolm, Clara Poupault, Miljan Kuljanin, Kristen M. John, Douglas E. Biancur, Brandon Chen, Nupur K. Das, Kristen E. Lowder, Connor J. Hennessey, Wesley Huang, Annan Yang, Yatrik M. Shah, Jonathan A. Nowak, Andrew J. Aguirre, Joseph D. Mancias. https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0043/704854

Coordinated transcriptional and catabolic programs support iron dependent adaptation to RAS-MAPK pathway inhibition in pancreatic cancer – Mirunalini Ravichandran, Jingjie Hu, Charles Cai, Nathan P. Ward, Anthony Venida, Callum Foakes, Miljan Kuljanin, Annan Yang, Connor J. Hennessey, Yang Yang, Brandon R. Desousa, Gilles Rademaker, Annelot A.L. Staes, Zeynep Cakir, Isha H. Jain, Andrew J. Aguirre, Joseph D. Mancias, Yin Shen, Gina M. DeNicola, Rushika M. Perera. https://aacrjournals.org/cancerdiscovery/article-abstract/doi/10.1158/2159-8290.CD-22-0044/706733

Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa‐Porthos axis in Drosophila – Shamsi Emtenani, Elliot T Martin, Attila Gyoergy, Julia Bicher, Jakob-Wendelin Genger, Thomas Köcher, Maria Akhmanova, Mariana Guarda, Marko Roblek, Andreas Bergthaler, Thomas R Hurd, Prashanth Rangan, Daria E Siekhaus. https://www.embopress.org/doi/full/10.15252/embj.2021109049


Cancer Immunometabolism


Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics – Qi Liu, Fangming Zhu, Xinnan Liu, Ying Lu, Ke Yao, Na Tian, Lingfeng Tong, David A. Figge, Xiuwen Wang, Yichao Han, Yakui Li, Yemin Zhu, Lei Hu, Yingning Ji, Nannan Xu, Dan Li, Xiaochuan Gu, Rui Liang, Guifang Gan, Lifang Wu, Ping Zhang, Tianle Xu, Hui Hu, Zeping Hu, Huji Xu, Dan Ye, Hui Yang, Bin Li and Xuemei Tong. https://www.nature.com/articles/s42255-022-00575-z

Leucine-tRNA-synthase-2-expressing B cells contribute to colorectal cancer immunoevasion – Zhiqiang Wang, Zhou Lu, Shengli Lin, Jie Xia, Ziwen Zhong, Zhangjuan Xie, Yun Xing, Jingbo Qie, Mengxia Jiao, Yifan Li, Haoyu Wen, Pengyuan Zhao, Dan Zhang, Pinghong Zhou, Jiawen Qian, Feifei Luo, Luman Wang, Hongxiu Yu, Jie Liu, Jie Gu, Ronghua Liu, Yiwei Chu. https://www.cell.com/immunity/fulltext/S1074-7613(22)00188-1

Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia – Jonas A. Wik, Azazul Chowdhury, Shrikant Kolan, Nasser E. Bastani, Gaoyang Li, Kazi Alam, Franco Grimolizzi, Bjørn S. Skålhegg. https://portlandpress.com/biochemj/article/479/11/1221/231349

Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells – Jian Gu, Jinren Zhou, Qiuyang Chen, Xiaozhang Xu, Ji Gao, Xiangyu Li, Qing Shao, Bo Zhou, Haoming Zhou, Song Wei, Qi Wang, Yuan Liang, Ling Lu. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00772-0


Miscellaneous


Metformin-induced reductions in tumor growth involves modulation of the gut microbiome – Lindsay A. Broadfield, Amna Saigal, Jake C. Szamosi, Joanne A. Hammill, Ksenia Bezverbnaya, Dongdong Wang, Jaya Gautam, Evangelia E. Tsakiridis, Fiorella Di Pastena, Jamie McNicol, Jianhan Wu, Saad Syed, James S.V. Lally, Amogelang R. Raphenya, Marie-Jose Blouin, Michael Pollak, Andrea Sacconi, Giovanni Blandino, Andrew G. McArthur, Jonathan D. Schertzer. https://www.sciencedirect.com/science/article/pii/S2212877822000679

An exercise-inducible metabolite that suppresses feeding and obesity – Veronica L. Li, Yang He, Kévin Contrepois, Hailan Liu, Joon T. Kim, Amanda L. Wiggenhorn, Julia T. Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H. Zushin, Robert S. Jansen, Basil Michael, Kang Yong Loh, Andrew C. Yang, Christian S. Carl, Christian T. Voldstedlund, Wei Wei, Stephanie M. Terrell, Benjamin C. Moeller, Rick M. Arthur, Gareth A. Wallis, Koen van de Wetering, Andreas Stahl, Bente Kiens, Erik A. Richter, Steven M. Banik, Michael P. Snyder, Yong Xu and Jonathan Z. Long. https://www.nature.com/articles/s41586-022-04828-5


Reviews


Ribosome biogenesis and the cellular energy economy – David Shore, Benjamin Albert. https://www.cell.com/current-biology/fulltext/S0960-9822(22)00719-9

Ferroptosis at the intersection of lipid metabolism and cellular signaling – Deguang Liang, Alexander M. Minikes, Xuejun Jiang. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00260-X

Shaping fuel utilization by mitochondria – Lukas Alan, Luca Scorrano. https://www.cell.com/current-biology/fulltext/S0960-9822(22)00765-5

Therapeutic Targeting of Tumor Cells and Tumor Immune Microenvironment Vulnerabilities – Balaraman Kalyanaraman, Gang Cheng, Micael Hardy. https://www.frontiersin.org/articles/10.3389/fonc.2022.816504/full

Fatty acid synthase: a druggable driver of breast cancer brain metastasis – Javier A. Menendez and Ruth Lupu. https://www.tandfonline.com/doi/full/10.1080/14728222.2022.2077189


Comments


NAD+ regeneration drives cancer cell proliferation – Xu Han and M. Celeste Simon. https://www.nature.com/articles/s42255-022-00579-9

YAP/TAZ–TEAD link angiogenesis to nutrients – Roxana E. Oberkersch and Massimo M. Santoro. https://www.nature.com/articles/s42255-022-00579-9

TCA cycle off, ATF4 on for metabolic homeostasis – Durga Mahor, Rishikesh Pandey, Vinay Bulusu. https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(22)00065-2

Research is a process – Sarah-Maria Fendt. https://www.nature.com/articles/s41556-022-00954-4

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