Metabolist – November 2022


AMPK


AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity – Qian Zhang, Shengduo Liu, Chen-Song Zhang, Qirou Wu, Xinyuan Yu, Ruyuan Zhou, Fansen Meng, Ailian Wang, Fei Zhang, Shasha Chen, Xiaojian Wang, Lei Li, Jun Huang, Yao-Wei Huang, Jian Zou, Jun Qin, Tingbo Liang, Xin-Hua Feng, Sheng-Cai Lin, Pinglong Xu. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)01054-1

circPRKAA1 activates a Ku80/Ku70/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells – Qidong Li, Hanhui Yao, Yichun Wang, Yang Wu, Rick F. Thorne, Youming Zhu, Mian Wu, Lianxin Liu. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01581-9

AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis – Yanan Wang, Mengjun Luo, Fan Wang, Yu Tong, Linfeng Li, Yu Shu, Ke Qiao, Lei Zhang, Guoquan Yan, Jing Liu, Hongbin Ji, Youhua Xie, Yonglong Zhang, Wei-Qiang Gao and Yanfeng Liu. https://www.nature.com/articles/s41467-022-34747-y

AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology – Lisa Tilokani, Fiona M. Russell, Stevie Hamilton, Daniel M. Virga, Mayuko Segawa, Vincent Paupe, Anja V. Gruszczyk, Margherita Protasoni, Luis-Carlos Tabara, Mark Johnson, Hanish Anand, Michael P. Murphy, D. Grahame Hardie, Franck Polleux, Julien Prudent. https://www.science.org/doi/full/10.1126/sciadv.abo7956

The phosphorylation of AMPKβ1 is critical for increasing autophagy and maintaining mitochondrial homeostasis in response to fatty acids – Eric M. Desjardins, Brennan K. Smith, Emily A. Day, Serge Ducommun, Matthew J. Sanders, Joshua P. Nederveen, Rebecca J. Ford, Stephen L. Pinkosky, Logan K. Townsend, Robert M. Gutgesell, Rachel Lu, Kei Sakamoto and Gregory R. Steinberg. https://www.pnas.org/doi/10.1073/pnas.2119824119


mTOR


Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex – McNamara MC, Hosios AM, Torrence ME, Zhao T, Fraser C, Wilkinson M, Kwiatkowski DJ, Henske EP, Wu CL, Sarosiek KA, Valvezan AJ, Manning BD. https://www.cell.com/iscience/fulltext/S2589-0042(22)01730-8

An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss – Kaushal Asrani, Juhyung Woo, Adrianna A. Mendes, Ethan Schaffer, Thiago Vidotto, Clarence Rachel Villanueva, Kewen Feng, Lia Oliveira, Sanjana Murali, Hans B. Liu, Daniela C. Salles, Brandon Lam, Pedram Argani and Tamara L. Lotan. https://www.nature.com/articles/s41467-022-34617-7

mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters – Yuanhui Liu, Nancy G. Azizian, Delaney K. Sullivan and Yulin Li. https://www.nature.com/articles/s41467-022-34890-6

An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma – Odai Darawshi, Barbara Muz, Shiri Gershon Naamat, Bellam Praveen, Mohamed Mahameed, Karin Goldberg, Priya Dipta, Miriam Shmuel, Francesca Forno, Shatha Boukeileh, Hadas Pahima, Julia Hermann, Marc S. Raab, Alexandra M. Poos, Niels Weinhold, Chaggai Rosenbluh, Moshe E. Gatt, Wilhelm Palm, Abdel Kareem Azab and Boaz Tirosh. https://www.nature.com/articles/s41419-022-05421-4


Starvation/metabolic stress


Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress – Ronghui Yang, Chuanzhen Yang, Lingdi Ma, Yiliang Zhao, Zihao Guo, Jing Niu, Qiaoyun Chu, Yingmin Ma and Binghui Li. https://www.nature.com/articles/s41467-022-34850-0

Phosphoproteomics revealed cellular signals immediately responding to disruption of cancer amino acid homeostasis induced by inhibition of L-type amino acid transporter 1 – Hiroki Okanishi, Ryuichi Ohgaki, Minhui Xu, Hitoshi Endou and Yoshikatsu Kanai. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00295-8

Carbon starvation, senescence and specific mitochondrial stresses, but not nitrogen starvation and general stresses, are major triggers for mitophagy in Arabidopsis – Sylwia M. Kacprzak and Olivier Van Aken. https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2054039

COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism – Yetong Feng, Jiayi Xu, Mengjiao Shi, Rongrong Liu, Lei Zhao, Xin Chen, Miaomiao Li, Yaping Zhao, Jiahui Chen, Wenjing Du and Pengfei Liu. https://www.nature.com/articles/s41419-022-05430-3


Glucose metabolism


Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth – Zheng Wang, Min Li, Hongfei Jiang, Shudi Luo, Fei Shao, Yan Xia, Mengke Yang, Xiangle Ren, Tong Liu, Meisi Yan, Xu Qian, Haiyan He, Dong Guo, Yuran Duan, Ke Wu, Lei Wang, Guimei Ji, Yuli Shen, Lin Li, Peixiang Zheng, Bofei Dong, Jing Fang, Min Zheng, Tingbo Liang, Haitao Li, Rilei Yu, Daqian Xu and Zhimin Lu. https://www.nature.com/articles/s41556-022-01009-4

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy – Kimberley McGrail, Paula Granado-Martínez, Rosaura Esteve-Puig, Sara García-Ortega, Yuxin Ding, Sara Sánchez-Redondo, Berta Ferrer, Javier Hernandez-Losa, Francesc Canals, Anna Manzano, Aura Navarro-Sabaté, Ramón Bartrons, Oscar Yanes, Mileidys Pérez-Alea, Eva Muñoz-Couselo, Vicenç Garcia-Patos and Juan A. Recio

https://www.nature.com/articles/s41467-022-34907-0

ALKBH5-Mediated m6A Demethylation of GLUT4 mRNA Promotes Glycolysis and Resistance to HER2-Targeted Therapy in Breast Cancer – Hao Liu, Hui Lyu, Guanmin Jiang, Danyang Chen, Sanbao Ruan, Shuang Liu, Lukun Zhou, Minqiang Yang, Shanshan Zeng, Zhimin He, Hongsheng Wang, Hongsheng Li, Guopei Zheng, Bolin Liu. https://aacrjournals.org/cancerres/article-abstract/82/21/3974/709951

GLUT1 is a Highly Efficient L-Fucose Transporter – Bobby G. Ng, Paulina Sosicka, Zhijie Xia, Hudson H. Freeze. https://www.jbc.org/article/S0021-9258(22)01181-4

Mutual regulation between phosphofructokinase 1 platelet isoform and VEGF promotes glioblastoma tumor growth – Je Sun Lim, YuJie Shi, Su Hwan Park, So Mi Jeon, Chuanbao Zhang, Yun-Yong Park, Rui Liu, Jing Li, Wan-Seob Cho, Linyong Du and Jong-Ho Lee. https://www.nature.com/articles/s41419-022-05449-6

Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade – Michal A. Stanczak, Natalia Rodrigues Mantuano, Nicole Kirchhammer, David E. Sanin, Francis Jacob, Ricardo Coelho, Arun V. Everest-Dass, Jinyu Wang, Marcel P. Trefny, Gianni Monaco, Anne Bärenwaldt, Melissa A. Gray, Adam Petrone, Abhishek S. Kashyap, Katharina Glatz, Benjamin Kasenda, Karl Normington, James Broderick, Li Peng, Oliver M.T. Pearce, Erika L. Pearce, Carolyn R. Bertozzi, Alfred Zippelius, Heinz Läubli. https://www.science.org/doi/abs/10.1126/scitranslmed.abj1270


Amino acid metabolism


Cancer cell survival depends on collagen uptake into tumor-associated stroma – Kuo-Sheng Hsu, James M. Dunleavey, Christopher Szot, Liping Yang, Mary Beth Hilton, Karen Morris, Steven Seaman, Yang Feng, Emily M. Lutz, Robert Koogle, Francesco Tomassoni-Ardori, Saurabh Saha, Xiaoyan M. Zhang, Enrique Zudaire, Pradip Bajgain, Joshua Rose, Zhongyu Zhu, Dimiter S. Dimitrov, Frank Cuttitta, Nancy J. Emenaker, Lino Tessarollo and Brad St. Croix. https://www.nature.com/articles/s41467-022-34643-5

Branched-chain amino acid catabolism breaks glutamine addiction to sustain hepatocellular carcinoma progression – Dongdong Yang, Haiying Liu, Yongping Cai, Kangyang Lu, Xiuying Zhong, Songge Xing, Wei Song, Yaping Zhang, Ling Ye, Xia Zhu, Ting Wang, Pinggen Zhang, Shi-Ting Li, Jiaqian Feng, Weidong Jia, Huafeng Zhang, Ping Gao. https://www.sciencedirect.com/science/article/pii/S2211124

Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells – Christopher J. Halbrook, Galloway Thurston, Seth Boyer, Cecily Anaraki, Jennifer A. Jiménez, Amy McCarthy, Nina G. Steele, Samuel A. Kerk, Hanna S. Hong, Lin Lin, Fiona V. Law, Catherine Felton, Lorenzo Scipioni, Peter Sajjakulnukit, Anthony Andren, Alica K. Beutel, Rima Singh, Barbara S. Nelson, Fran Van Den Bergh, Abigail S. Krall, Peter J. Mullen, Li Zhang, Sandeep Batra, Jennifer P. Morton, Ben Z. Stanger, Heather R. Christofk, Michelle A. Digman, Daniel A. Beard, Andrea Viale, Ji Zhang, Howard C. Crawford, Marina Pasca di Magliano, Claus Jorgensen and Costas A. Lyssiotis. https://www.nature.com/articles/s43018-022-00463-1

Inhibition of glutaminolysis restores mitochondrial function in senescent stem cells – Debanik Choudhury, Na Rong, Izuagie Ikhapoh, Nika Rajabian, Georgios Tseropoulos, Yulun Wu, Pihu Mehrotra, Ramkumar Thiyagarajan, Aref Shahini, Kenneth L. Seldeen, Bruce R. Troen, Pedro Lei, Stelios T. Andreadis. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01622-9


Lipid / propionate /acetate metabolism


Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression – Zhongchi Li, Vivien Low, Valbona Luga, Janet Sun, Ethan Earlie, Bobak Parang, Kripa Shobana Ganesh, Sungyun Cho, Jennifer Endress, Tanya Schild, Mengying Hu, David Lyden, Wenbing Jin, Chunjun Guo, Noah Dephoure, Lewis C. Cantley, Ashley M. Laughney and John Blenis. https://www.nature.com/articles/s41467-022-33862-0

Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer – Juho Pirhonen, Ábel Szkalisity, Jaana Hagström, Yonghyo Kim, Ede Migh, Mária Kovács, Maarit Hölttä, Johan Peränen, Hanna Seppänen, Caj Haglund, Jeovanis Gil, Melinda Rezeli, Johan Malm, Peter Horvath, György Markó-Varga, Pauli Puolakkainen, Elina Ikonen. https://aacrjournals.org/cancerres/article-abstract/82/21/3932/709964

Acetyl-CoA carboxylase 1 depletion suppresses de novo fatty acid synthesis and mitochondrial β-oxidation in castration-resistant prostate cancer cells – Shaoyou Liu, Jiarun Lai, Yuanfa Feng, Yangjia Zhuo, Hui Zhang, Yupeng Chen, Jinchuang Li, Xinyue Mei, Yanting Zeng, Jiaming Su, Yulin Deng, Funeng Jiang, Shengbang Yang, Huijing Tan, Chi Tin Hon, Sun Wei, Zhaodong Han, Fen Wang, Weide Zhong. https://www.jbc.org/article/S0021-9258(22)01163-2/fulltext

Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis – Sujin Park, Dirk Mossmann, Qian Chen, Xueya Wang, Eva Dazert, Marco Colombi, Alexander Schmidt, Brendan Ryback, Charlotte K.Y. Ng, Luigi M. Terracciano, Markus H. Heim, Michael N. Hall. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)01055-3


Mitochondrial metabolism and impairment


Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells – Patricia Altea-Manzano, Anke Vandekeere, Joy Edwards-Hicks, Mar Roldan,  Emily Abraham, Xhordi Lleshi, Ania Naila Guerrieri, Domenica Berardi, Jimi Wills, Jair Marques Junior, Asimina Pantazi, Juan Carlos Acosta, Rosario M. Sanchez-Martin, Sarah-Maria Fendt, Miguel Martin-Hernandez, Andrew J. Finch. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00962-5

Mitochondrial dysfunction triggers actin polymerization necessary for rapid glycolytic activation – Rajarshi Chakrabarti, Tak Shun Fung, Taewook Kang, Pieti W. Elonkirjo, Anu Suomalainen, Edward J. Usherwood, Henry N. Higgs. https://rupress.org/jcb/article/221/11/e202201160/213462

Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation – Hae J Park, Mark A Gregory, Vadym Zaberezhnyy, Andrew Goodspeed, Craig T Jordan, Jeffrey S Kieft, James DeGregori. https://elifesciences.org/articles/79940


Cancer Immunometabolism


GAB functions as a bioenergetic and signalling gatekeeper to control T cell inflammation – Siwen Kang, Lingling Liu, Tingting Wang, Matthew Cannon, Penghui Lin, Teresa W-M Fan, David A Scott, Hsin-Jung Joyce Wu, Andrew N Lane, Ruoning Wang.. https://www.nature.com/articles/s42255-022-00638-1

A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes – Leire Pedrosa, Carles Foguet, Helena Oliveres, Iván Archilla, Marta García de Herreros, Adela Rodríguez, Antonio Postigo, Daniel Benítez-Ribas, Jordi Camps, Miriam Cuatrecasas, Antoni Castells, Aleix Prat, Timothy M Thomson, Joan Maurel, Marta Cascante. https://www.frontiersin.org/articles/10.3389/fimmu.2022.926304/full

CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation – Juan Fernández-García, Fabien Franco, Sweta Parik, Patricia Altea-Manzano, Antonino Alejandro Pane, Dorien Broekaert, Joke van Elsen, Ines Vermeire, Tessa Schalley, Mélanie Planque, Thomas van Brussel, Rogier Schepers, Elodie Modave, Tobias K. Karakach, Peter Carmeliet, Diether Lambrechts, Ping-Chih Ho, Sarah-Maria Fendt. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01510-8

OXPHOS promotes apoptotic resistance and cellular persistence in TH17 cells in the periphery and tumor microenvironment – Hanna S. Hong, Nneka E. Mbah, Mengrou Shan, Kristen Loesel, Lin Lin, Peter Sajjakulnukit, Luis O. Correa, Anthony Andren, Jason Lin, Atsushi Hayashi, Brian Magnuson, Judy Chen, Zhaoheng Li, Yuying Xie, Li Zhang, Daniel R. Goldstein, Shannon A. Carty, Yu Leo Lei, Anthony W. Opipari, Rafael J. Argüello, Ilona Kryczek, Nobuhiko Kamada, Weiping Zou, Luigi Franchi, Costas A. Lyssiotis. https://www.science.org/doi/full/10.1126/sciimmunol.abm8182


Miscellaneous


Anti-diabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1 – Yiyan Chen, Min Li, Yanying Yang, Yan Lu, Xiaoying Li. https://www.jbc.org/article/S0021-9258(22)01121-8

Computed tomography-measured body composition and survival in rectal cancer patients: a Swedish cohort study – Angeliki Kotti, Annica Holmqvist, Mischa Woisetschläger and Xiao-Feng Sun. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00297-6

An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination – Danna Sheinboim, Shivang Parikh, Paulee Manich, Irit Markus, Sapir Dahan, Roma Parikh, Elisa Stubbs, Gali Cohen, Valentina Zemser-Werner, Rachel E. Bell, Sara Arciniegas Ruiz, Ruth Percik, Ronen Brenner, Stav Leibou, Hananya Vaknine, Gali Arad, Yariv Gerber, Lital Keinan-Boker, Tal Shimony, Lior Bikovski, Nir Goldstein, Keren Constantini, Sapir Labes, Shimonov Mordechai, Hila Doron, Ariel Lonescu, Tamar Ziv, Eran Nizri, Guy Choshen, Hagit Eldar-Finkelman, Yuval Tabach, Aharon Helman, Shamgar Ben-Eliyahu, Neta Erez, Eran Perlson, Tamar Geiger, Danny Ben-Zvi, Mehdi Khaled, Yftach Gepner, Carmit Levy. https://aacrjournals.org/cancerres/article/82/22/4164/710131

Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature – Olivia Lombardi, Ran Li, Silvia Halim, Hani Choudhry, Peter J. Ratcliffe, David R. Mole. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01523-6


Reviews


Metabolic determinants of tumour initiation – Julia S. Brunner and Lydia W. S. Finley. https://www.nature.com/articles/s41574-022-00773-5

Metabolite activation of tumorigenic signaling pathways in the tumor microenvironment – Vivien Low, Zhongchi Li, John Blenis. https://www.science.org/doi/abs/10.1126/scisignal.abj4220

Metabolic communication in the tumour–immune microenvironment – Kung-Chi Kao, Stefania Vilbois, Chin-Hsien Tsai and Ping-Chih Ho. https://www.nature.com/articles/s41556-022-01002-x

Targeting the DNA damage response and repair in cancer through nucleotide metabolism – Thomas Helleday,Sean G. Rudd. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13227

Challenges and Emerging Opportunities for Targeting mTOR in Cancer – Kris C. Wood; J. Silvio Gutkind. https://aacrjournals.org/cancerres/article-abstract/82/21/3884/709952

Emerging metabolomic tools to study cancer metastasis – Luiza Martins Nascentes Melo, Nicholas P. Lesner, Marie Sabatier, Jessalyn M. Ubellacker, Alpaslan Tasdogan. https://www.cell.com/trends/cancer/fulltext/S2405-8033(22)00156-X

Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment – Petya Apostolova, Erika L. Pearce. https://www.sciencedirect.com/science/article/abs/pii/S1471490622002137

Src: coordinating metabolism in cancer – Sara G. Pelaz and Arantxa Tabernero. https://www.nature.com/articles/s41388-022-02487-4

Glycan quality control in and out of the endoplasmic reticulum of mammalian cells – Yoichiro Harada, Yuki Ohkawa, Kento Maeda, Naoyuki Taniguchi. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16185

Targeting adaptive cellular responses to mitochondrial bioenergetic deficiencies in human disease – Christopher F. Bennett, Conor T. Ronayne, Pere Puigserver. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16195


Comments / other


Metabolic phosphatase moonlights for proteins – Scott A. Gerber & Arminja N. Kettenbach. https://www.nature.com/articles/s41556-022-00993-x

Acetyl-CoA, protein acetylation, and liver cancer – Zhengming Wu, Kun-Liang Guan. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)01015-2

Tumour-derived d-2HG blocks T cell cytotoxicity – Joseph Willson. https://www.nature.com/articles/s41568-022-00534-6

D-2HG comes out of its shell: Metabolic effects on the immune environment – Juan Manuel Schvartzman, Andrew M. Intlekofer. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)01067-X

Aerobic Glycolysis Promotes an NF-κB–Mediated Increase in PD-L1 Expression. https://aacrjournals.org/cancerdiscovery/article-abstract/12/11/OF5/709972

Cell scientist to watch – Lena Pernas. https://journals.biologists.com/jcs/article/135/21/jcs260704/278594

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