MetaboList – July 2022


Nutrient sensing/starvation


Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila – Xin Gu, Patrick Jouandin, Pranav V. Lalgudi, Rich Binari, Max L. Valenstein, Michael A. Reid, Annamarie E. Allen, Nolan Kamitaki, Jason W. Locasale, Norbert Perrimon and David M. Sabatini. https://www.nature.com/articles/s41586-022-04960-2

Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila – Hina Kosakamoto, Naoki Okamoto, Hide Aikawa, Yuki Sugiura, Makoto Suematsu, Ryusuke Niwa, Masayuki Miura and Fumiaki Obata. https://www.nature.com/articles/s42255-022-00608-7

Structure of the nutrient-sensing hub GATOR2 – Max L. Valenstein, Kacper B. Rogala, Pranav V. Lalgudi, Edward J. Brignole, Xin Gu, Robert A. Saxton, Lynne Chantranupong, Jonas Kolibius, Jan-Philipp Quast and David M. Sabatini. https://www.nature.com/articles/s41586-022-04939-z

DRAM‐4 and DRAM‐5 are compensatory regulators of autophagy and cell survival in nutrient‐deprived conditions – Valentin J. A. Barthet, Michaela Mrschtik, Elzbieta Kania, David G. McEwan, Dan Croft, James O’Prey, Jaclyn S. Long, Kevin M. Ryan. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16365

Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter – Danielle L. Schmitt, Stephanie D. Curtis, Anne C. Lyons, Jin-fan Zhang, Mingyuan Chen, Catherine Y. He, Sohum Mehta, Reuben J. Shaw and Jin Zhang. https://www.nature.com/articles/s41467-022-31190-x


Starvation – UPR


The amino acid sensor GCN2 suppresses Terminal Oligopyrimidine (TOP) mRNA translation via La-related Protein 1 (LARP1) – Zeenat Farooq, Fedho Kusuma, Phillip Burke, Catherine R. Dufour, Duckgue Lee, Negar Tabatabaei, Phoenix Toboz, Ernest Radovani, Jack Greenblatt, Jalees Rehman, Jacob Class, Arkady Khoutorsky, Bruno D. Fonseca, Justin M. Richner, Eloi Mercier, Guillaume Bourque, Vincent Giguère, Arvind R. Subramaniam, Jaeseok Han, Soroush Tahmasebi. https://www.jbc.org/article/S0021-9258(22)00719-0/fulltext

Activation of the canonical ER Stress IRE1-XBP1 Pathway by Insulin Regulates Glucose and Lipid Metabolism – Jinghua Peng, Caolitao Qin, Balamurugan Ramatchandirin, Alexia Pearah, Shaodong Guo, Mehboob Hussain, Liqing Yu, Fredric E. Wondisford, Ling He. https://www.jbc.org/article/S0021-9258(22)00725-6

FKBP11 rewires UPR signaling to promote glucose homeostasis in type 2 diabetes and obesity – Hilde Herrema, Dongxian Guan, Jae Won Choi, Xudong Feng, Mario Andres Salazar Hernandez, Farhana Faruk, Thomas Auen, Eliza Boudett, Rongya Tao, Hyonho Chun, Umut Ozcan. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00227-3

Activated amino acid response pathway generates apatinib resistance by reprograming glutamine metabolism in non-small-cell lung cancer – Xiaoshu Zhou, Rui Zhou, Xinrui Rao, Jiaxin Hong, Qianwen Li, Xiaohua Jie, Jian Wang, Yingzhuo Xu, Kuikui Zhu, Zhenyu Li and Gang Wu. https://www.nature.com/articles/s41419-022-05079-y


mTOR


Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate – Swantje Liedmann, Xueyan Liu, Clifford S. Guy, Jeremy Chase Crawford, Diego A. Rodriguez, Duygu Kuzuoğlu-Öztürk, Ao Guo, Katherine C. Verbist, Jamshid Temirov, Mark J. Chen, Davide Ruggero, Hui Zhang, Paul G. Thomas, Douglas R. Green. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00327-6

Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR – Dawid Krokowski, Raul Jobava, Krzysztof J. Szkop, Chien-Wen Chen, Xu Fu, Sarah Venus, Bo-Jhih Guan, Jing Wu, Zhaofeng Gao, Wioleta Banaszuk, Marek Tchorzewski, Tingwei Mu, Phil Ropelewski, William C. Merrick, Yuanhui Mao, Aksoylu Inci Sevval, Helen Miranda, Shu-Bing Qian, Maria Manifava, Nicholas T. Ktistakis, Anastasios Vourekas, Eckhard Jankowsky, Ivan Topisirovic, Ola Larsson, Maria Hatzoglou. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00894-4


Hypoxia


Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression – Mohamed A. Abu el Maaty, Julie Terzic, Céline Keime, Daniela Rovito, Régis Lutzing, Darya Yanushko, Maxime Parisotto, Elise Grelet, Izzie Jacques Namer, Véronique Lindner, Gilles Laverny, Daniel Metzger. https://www.science.org/doi/full/10.1126/sciadv.abo229

Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy – Shijun Ma, Yue Zhao, Wee Chyan Lee, Li-Teng Ong, Puay Leng Lee, Zemin Jiang, Gokce Oguz, Zhitong Niu, Min Liu, Jian Yuan Goh, Wenyu Wang, Matias A. Bustos, Sidse Ehmsen, Adaikalavan Ramasamy, Dave S. B. Hoon, Henrik J. Ditzel, Ern Yu Tan, Qingfeng Chen and Qiang Yu. https://www.nature.com/articles/s41467-022-31764-9


IDH


Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors – Ali Vaziri-Gohar, Joel Cassel, Farheen S. Mohammed, Mehrdad Zarei, Jonathan J. Hue, Omid Hajihassani, Hallie J. Graor, Yellamelli V. V. Srikanth, Saadia A. Karim, Ata Abbas, Erin Prendergast, Vanessa Chen, Erryk S. Katayama, Katerina Dukleska, Imran Khokhar, Anthony Andren, Li Zhang, Chunying Wu, Bernadette Erokwu, Chris A. Flask, Mahsa Zarei, Rui Wang, Luke D. Rothermel, Andrea M. P. Romani, Jessica Bowers, Robert Getts, Curtis Tatsuoka, Jennifer P. Morton, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Joseph M. Salvino, Jonathan R. Brody and Jordan M. Winter. https://www.nature.com/articles/s43018-022-00393-y

Accumulation of oncometabolite D-2-Hydroxyglutarate by SLC25A1 inhibition: A metabolic strategy for induction of HR-ness and radiosensitivity – Kexu Xiang, Christian Kalthoff, Corinna Münch, Verena Jendrossek and Johann Matschke. https://www.nature.com/articles/s41419-022-05098-9


Glucose/lactate metabolism


Pyruvate Kinase M1 Suppresses Development and Progression of Prostate Adenocarcinoma – Shawn M. Davidson; Daniel R. Schmidt; Julia E. Heyman; James P. O’Brien; Amy C. Liu; William J. Israelsen; Talya L. Dayton; Raghav Sehgal; Roderick T. Bronson; Elizaveta Freinkman; Howard H. Mak; Giuseppe Nicolò Fanelli; Scott Malstrom; Gary Bellinger; Arkaitz Carracedo; Pier Paolo Pandolfi; Kevin D. Courtney; Abhishek Jha; Ronald A. DePinho; James W. Horner; Craig J. Thomas; Lewis C. Cantley; Massimo Loda; Matthew G. Vander Heiden. https://aacrjournals.org/cancerres/article/82/13/2403/705036/

Riboregulation of Enolase 1 activity controls glycolysis and embryonic stem cell differentiation – Ina Huppertz, Joel I. Perez-Perri, Panagiotis Mantas, Thileepan Sekaran, Thomas Schwarzl, Francesco Russo, Dunja Ferring-Appel, Zuzana Koskova, Lyudmila Dimitrova-Paternoga, Eleni Kafkia, Janosch Hennig, Pierre A. Neveu, Kiran Patil, Matthias W. Hentze. https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00486-5

G6PD-mediated increase in de novo NADP+ biosynthesis promotes antioxidant defense and tumor metastasis – Yang Zhang, Yi Xu, Wenyun Lu, Jinyang Li, Sixiang Yu, Eric J. Brown, Ben Z. Stanger, Joshua D. Rabinowitz, Xiaolu Yang. https://www.science.org/doi/full/10.1126/sciadv.abo040

The hexokinase “HKDC1” interaction with the mitochondria is essential for liver cancer progression – Md. Wasim Khan, Alexander R. Terry, Medha Priyadarshini, Vladimir Ilievski, Zeenat Farooq, Grace Guzman, Jose Cordoba-Chacon, Issam Ben-Sahra, Barton Wicksteed and Brian T. Layden. https://www.nature.com/articles/s41419-022-04999-z

Lactate promotes metastasis of normoxic colorectal cancer stem cells through PGC-1α-mediated oxidative phosphorylation – Shuang Liu, Hui Zhao, Yibing Hu, Chang Yan, Yulong Mi, Xiaolan Li, Deding Tao and Jichao Qin. https://www.nature.com/articles/s41419-022-05111-1


Amino acid metabolism


Tumoral microenvironment prevents de novo asparagine biosynthesis in B cell lymphoma, regardless of ASNS expression – Manuel Grima-Reyes, Ashaina Vandenberghe, Ivan Nemazanyy, Pauline Meola, Rachel Paul, Julie Reverso-Meinietti, Adriana Martinez-Turtos, Nicolas Nottet, Wai-Kin Chan, Philip L. Lorenzi, Sandrine Marchetti, Jean-Ehrland Ricci, Johanna Chiche. https://www.science.org/doi/full/10.1126/sciadv.abn6491

Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma – Bo Zhang, Hui Peng, Mi Zhou, Lei Bao, Chenliang Wang, Feng Cai, Hongxia Zhang, Jennifer E. Wang, Yanling Niu, Yan Chen, Yijie Wang, Kimmo J. Hatanpaa, John A. Copland, Ralph J. DeBerardinis, Yingfei Wang, Weibo Luo. https://aacrjournals.org/cancerres/article-abstract/82/13/2388/705041

Cyclocreatine Suppresses Creatine Metabolism and Impairs Prostate Cancer Progression – Rachana Patel, Catriona A. Ford, Lisa Rodgers, Linda K. Rushworth, Janis Fleming, Ernest Mui, Tong Zhang, David Watson, Victoria Lynch, Gillian Mackay, David Sumpton, Owen J. Sansom, Johan Vande Voorde, Hing Y. Leung. https://aacrjournals.org/cancerres/article/82/14/2565/706947

Synthetic Essentiality of Tryptophan 2,3-Dioxygenase 2 in APC-Mutated Colorectal Cancer – Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A. LaBella, Jing Li, Denise J. Spring, Di Zhao, Y. Alan Wang, Ronald A. DePinho. https://aacrjournals.org/cancerdiscovery/article-abstract/12/7/1702/705207

Autophagy loss impedes cancer-associated fibroblast activation via downregulating proline biosynthesis – Jingru Bai, Tong Liu, Bo Tu, Meng Yuan, Zhaoqi Shu, Minghe Fan, Sihan Huo, Yuyao Guo, Lina Wang, Hua Wang and Ying Zhao. https://www.tandfonline.com/doi/abs/10.1080/15548627.2022.2093026

Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance – Jiliang Xia, Jingyu Zhang, Xuan Wu, Wanqing Du, Yinghong Zhu, Xing Liu, Zhenhao Liu, Bin Meng, Jiaojiao Guo, Qin Yang, Yihui Wang, Qinglin Wang, Xiangling Feng, Guoxiang Xie, Yi Shen, Yanjuan He, Juanjuan Xiang, Minghua Wu, Gang An, Lugui Qiu, Wei Jia and Wen Zhou. https://www.nature.com/articles/s41467-022-31248-w


Lipid metabolism


PI3K drives the de novo synthesis of coenzyme A from vitamin B5 – Christian C. Dibble, Samuel A. Barritt, Grace E. Perry, Evan C. Lien, Renee C. Geck, Sarah E. DuBois-Coyne, David Bartee, Thomas T. Zengeya, Emily B. Cohen, Min Yuan, Benjamin D. Hopkins, Jordan L. Meier, John G. Clohessy, John M. Asara, Lewis C. Cantley and Alex Toker. https://www.nature.com/articles/s41586-022-04984-8

Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers – Mohammed I. Y. Elmallah, Pablo Ortega-Deballon, Laure Hermite, Jean-Paul Pais-De-Barros, Jessica Gobbo, Carmen Garrido. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13223

Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer – Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L. Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett, Katerina Politi, Sandra L. Starnes, Daniele Lorenzini, Maria Gabriela Raso, Luisa M. Solis Soto, Carmen Behrens, Humam Kadara, Boning Gao, Ignacio I. Wistuba, John D. Minna, Jeffrey G. McDonald and Pier Paolo Scaglioni. https://www.nature.com/articles/s41467-022-31963-4


Nucleotides


Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors – Melvin Pan, Christiane Zorbas, Maki Sugaya, Kensuke Ishiguro, Miki Kato 1, Miyuki Nishida, Hai-Feng Zhang, Marco M Candeias, Akimitsu Okamoto, Takamasa Ishikawa, Tomoyoshi Soga, Hiroyuki Aburatani, Juro Sakai, Yoshihiro Matsumura, Tsutomu Suzuki, Christopher G Proud, Denis L J Lafontaine, Tsuyoshi Osawa. https://www.nature.com/articles/s41467-022-31418-w

Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia – Joan So, Alexander C Lewis, Lorey K Smith, Kym Stanley, Rheana Franich, David Yoannidis, Lizzy Pijpers, Pilar Dominguez, Simon J Hogg, Stephin J Vervoort, Fiona C Brown, Ricky W Johnstone, Gabrielle McDonald, Danielle B Ulanet, Josh Murtie, Emily Gruber, Lev M Kats. https://www.embopress.org/doi/full/10.15252/emmm.202115203

Dihydroorotate dehydrogenase inhibition reveals metabolic vulnerability in chronic myeloid leukemia – Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta and Giuseppe Saglio. https://www.nature.com/articles/s41419-022-05028-9


Mitochondria and TCA


13C tracer analysis suggests extensive recycling of endogenous CO2 in vivo – Likun Duan, Daniel E. Cooper, Grace Scheidemantle, Jason W. Locasale, David G. Kirsch and Xiaojing Liu. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00287-8

Metabolic requirement for GOT2 in pancreatic cancer depends on environmental context – Samuel Kerk, Lin Lin, Amy L Myers, Damien J Sutton, Anthony Andren, Peter Sajjakulnukit, Li Zhang, Yaqing Zhang, Jennifer A Jiménez, Barbara S Nelson, Brandon Chen, Anthony Robinson, Galloway Thurston, Samantha B Kemp, Nina G Steele, Megan T Hoffman, Hui-Ju Wen, Daniel Long, Sarah E Ackenhusen, Johanna Ramos, Xiaohua Gao, Zeribe C Nwosu, Stefanie Galban, Christopher J Halbrook, David B Lombard, David R Piwnica-Worms, Haoqiang Ying, Marina Pasca di Magliano, Howard C Crawford , Yatrik M Shah, Costas A Lyssiotis. https://elifesciences.org/articles/73245

The mitochondrial enzyme FAHD1 regulates complex II activity in breast cancer cells and is indispensable for basal BT-20 cells in vitro – Max Holzknecht, Lena Guerrero-Navarro, Michele Petit, Eva Albertini, Elisabeth Damisch, Anna Simonini, Fernando Schmitt, Walther Parson, Heidelinde Fiegl, Alexander Weiss, Pidder Jansen-Duerr. https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14462


Miscellaneous


Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue – Alba Gonzalez-Franquesa, Pau Gama-Perez, Marta Kulis, Karolina Szczepanowska, Norma Dahdah, Sonia Moreno-Gomez, Ana Latorre-Pellicer, Rebeca Fernández-Ruiz, Antoni Aguilar-Mogas, Anne Hoffman, Erika Monelli, Sara Samino, Joan Miró-Blanch, GregorOemer, Xavier Duran, Estrella Sanchez-Rebordelo, Marc Schneebergerg, Merce Obac, Joel Montane, Giancarlo Castellano, Vicente Chapaprieta, Wenfei Sun, Lourdes Navarro, Ignacio Prieto, Carlos Castaño, Anna Novials, Ramon Gomis, Maria Monsalve, Marc Claret, Mariona Graupera, Guadalupe Soria, Christian Wolfrum, Joan Vendrell, Sonia Fernández-Veledo, Jose Antonio Enríque, Angel Carracedo, José Carlos Perales, Rubén Nogueiras, Laura Herrero, Aleksandra Trifunovi, Markus A.Keller, Oscar Yanes, Marta Sales-Pardo, Roger Guimerà, Matthias Blüher, José Ignacio Martín-Subero, Pablo M.Garcia-Roves. https://doi.org/10.1016/j.redox.2022.102353

Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity – Daniela D. Weber, Sepideh Aminzadeh-Gohari, Maheshwor Thapa, Anna-Sophia Redtenbacher, Luca Catalano, Tânia Capelôa, Thibaut Vazeille, Michael Emberger, Thomas K. Felder, René G. Feichtinger, Peter Koelblinger, Guido Dallmann, Pierre Sonveaux, Roland Lang and Barbara Kofler. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00288-7

The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib – Piotr Kobialka, Helena Sabata, Odena Vilalta, Leonor Gouveia, Ana Angulo-Urarte, Laia Muixí, Jasmina Zanoncello, Oscar Muñoz-Aznar, Nagore G Olaciregui, Lucia Fanlo, Anna Esteve-Codina, Cinzia Lavarino, Biola M Javierre, Veronica Celis, Carlota Rovira, Susana López-Fernández, Eulàlia Baselga, Jaume Mora, Sandra D Castillo, Mariona Graupera. https://www.embopress.org/doi/full/10.15252/emmm.202115619

FKBP11 rewires UPR signaling to promote glucose homeostasis in type 2 diabetes and obesity – Hilde Herrema, Dongxian Guan, Jae Won Choi, Xudong Feng, Mario Andres Salazar Hernandez, Farhana Faruk, Thomas Auen, Eliza Boudett, Rongya Tao, Hyonho Chun, Umut Ozcan. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00187-5


Reviews


Targeting mitochondrial metabolism for precision medicine in cancer – Lourdes Sainero-Alcolado, Judit Liaño-Pons, María Victoria Ruiz-Pérez and Marie Arsenian-Henriksson. https://www.nature.com/articles/s41418-022-01022-y

Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis – Elisa Donato, Andreas Trumpp. https://www.embopress.org/doi/full/10.15252/emmm.202216171

Polyamines in cancer: integrating organismal metabolism and antitumour immunity – Cassandra E. Holbert, Michael T. Cullen, Robert A. Casero Jr and Tracy Murray Stewart. https://www.nature.com/articles/s41568-022-00473-2

Scaling of biosynthesis and metabolism with cell size – Clotilde Cadart and Rebecca Heald. https://www.molbiolcell.org/doi/abs/10.1091/mbc.E21-12-0627

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

The Promise of Targeting Hypoxia to Improve Cancer Immunotherapy: Mirage or Reality? – Bassam Janji, Salem Chouaib. https://www.frontiersin.org/articles/10.3389/fimmu.2022.880810/full

Beyond controlling cell size: functional analyses of S6K in tumorigenesis – Xueji Wu, Wei Xie, Wenxuan Xie, Wenyi Wei and Jianping Guo. https://www.nature.com/articles/s41419-022-05081-4


Comments


Driving with Both Feet: Supplementing AKG While Inhibiting BCAT1 Leads to Synthetic Lethality in GBM – Noah Meurs, Deepak Nagrath. https://aacrjournals.org/cancerres/article-abstract/82/13/2354/705023

IFNα Potentiates Immune-Checkpoint Blockade by Rewiring Metabolic Cross-talk – Kung-Chi Kao, Alison Jaccard, Ping-Chih Ho. https://aacrjournals.org/cancerdiscovery/article-abstract/12/7/1615/705216

Akt protein boosts cancer metabolism through a two-pronged attack – Philipp Poeller and Almut Schulze. https://www.nature.com/articles/d41586-022-01603-4

Low Phosphoglycerate Dehydrogenase Levels Drive Metastatic Disseminationhttps://aacrjournals.org/cancerdiscovery/article-abstract/12/7/1611/705198

Colorectal Cancer Growth Is Reduced by the Ketone Body β-Hydroxybutyratehttps://aacrjournals.org/cancerdiscovery/article-abstract/12/7/OF15/705202

Ceramide Accumulation Induces the Integrated Stress Response in AMLhttps://aacrjournals.org/cancerdiscovery/article-abstract/12/7/OF14/705203

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