MetaboList – November 2021


Mitochondria and ROS


Fumarate is a terminal electron acceptor in the mammalian electron transport chain – Jessica B. Spinelli, Paul C. Rosen, Hans-Georg Sprenger, Anna M. Puszynska, Jessica L. Mann, Julian M. Roessler, Andrew L. Cangelosi, Antonia Henne, Kendall J. Condon, Tong Zhang, Tenzin Kunchok, Caroline A. Lewis, Navdeep S. Chandel, David M. Sabatini. https://www.science.org/doi/10.1126/science.abi7495
Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment – Simon Schwörer, Natalya N. Pavlova, Francesco V. Cimino, Bryan King, Xin Cai, Gina M. Sizemore and Craig B. Thompson. https://www.nature.com/articles/s42255-021-00480-x
Dynamic regulation of mitochondrial pyruvate metabolism is necessary for orthotopic pancreatic tumor growth – Nancy P Echeverri Ruiz, Vijay Mohan, Jinghai Wu, Sabina Scott, McKenzie Kreamer, Martin Benej, Tereza Golias, Ioanna Papandreou, Nicholas C Denko. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00275-4
Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II – Taiki Nagano, Yuto Awai, Shione Kuwaba, Taiichi Osumi, Kentaro Mio,  Tetsushi Iwasaki, and Shinji Kamada. https://www.molbiolcell.org/doi/10.1091/mbc.E21-05-0262?ai=s5&ui=2oy6&af=T
Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants – Alisha G. Lewis, Robert Caldwell, Jason V. Rogers, Maria Ingaramo, Rebecca Y. Wang, Ilya Soifer, David G. Hendrickson, R. Scott McIsaac, David Botstein, and Patrick A. Gibney. https://www.molbiolcell.org/doi/abs/10.1091/mbc.E21-06-0314
SLC25A1 promotes tumor growth and survival by reprogramming energy metabolism in colorectal cancer – Ying Yang, Jiaxing He, Bo Zhang, Zhansheng Zhang, Guozhan Jia, Shiqi Liu, Tao Wu, Xianli He and Nan Wang. https://www.nature.com/articles/s41419-021-04411-2
Molecular characteristics and tumorigenicity of ascites‐derived tumor cells: mitochondrial oxidative phosphorylation as a novel therapy target in ovarian cancer – Yi Ding, Vera Labitzky, Karen Legler, Minyue Qi, Udo Schumacher, Barbara Schmalfeldt, Christine Stürken, Leticia Oliveira-Ferrer. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13028

YAP1-mediated regulation of mitochondrial dynamics in IDH1 mutant gliomas – Shruti Patrick, Pruthvi Gowda, Kirti Lathoria, Vaishali Suri, Ellora Sen. https://journals.biologists.com/jcs/article-abstract/134/22/jcs259188/273515

Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia – Claudie Bosc, Estelle Saland, Aurélie Bousard, Noémie Gadaud, Marie Sabatier, Guillaume Cognet, Thomas Farge, Emeline Boet, Mathilde Gotanègre, Nesrine Aroua, Pierre-Luc Mouchel, Nathaniel Polley, Clément Larrue, Eléonore Kaphan, Muriel Picard, Ambrine Sahal, Latifa Jarrou, Marie Tosolini, Florian Rambow, Florence Cabon, Nathalie Nicot, Laura Poillet-Perez, Yujue Wang, Xiaoyang Su, Quentin Fovez, Jérôme Kluza, Rafael José Argüello, Céline Mazzotti, Hervé Avet-Loiseau, François Vergez, Jérôme Tamburini, Jean-Jacques Fournié, Ing S. Tiong, Andrew H. Wei, Tony Kaoma, Jean-Christophe Marine, Christian Récher, Lucille Stuani, Carine Joffre and Jean-Emmanuel Sarry
https://www.nature.com/articles/s43018-021-00264-y


Lipid metabolism


Dietary palmitic acid promotes a prometastatic memory via Schwann cells – Gloria Pascual, Diana Domínguez, Marc Elosúa-Bayes, Felipe Beckedorff, Carmelo Laudanna, Claudia Bigas, Delphine Douillet, Carolina Greco, Aikaterini Symeonidi, Inmaculada Hernández, Sara Ruiz Gil, Neus Prats, Coro Bescós, Ramin Shiekhattar, Moran Amit, Holger Heyn, Ali Shilatifard and Salvador Aznar Benitah. https://www.nature.com/articles/s41586-021-04075-0
Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis – Madeleine Dorsch, Manuela Kowalczyk, Mélanie Planque, Geronimo Heilmann, Sebastian Urban, Philip Dujardin, Jan Forster, Kristina Ueffing, Silke Nothdurft, Sebastian Oeck, Annika Paul, Sven T. Liffers, Farnusch Kaschani, Markus Kaiser, Alexander Schramm, Jens T. Siveke, Monte M. Winslow, Sarah-Maria Fendt, Perihan Nalbant, Barbara M. Grüner. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01542-4

Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma – Romain Riscal, Caroline J. Bull, Clementina Mesaros, Jennifer M. Finan, Madeleine Carens, Elaine S. Ho, Jimmy P. Xu, Jason Godfrey, Paul Brennan, Mattias Johansson, Mark P. Purdue, Stephen J. Chanock, Daniela Mariosa, Nicholas J. Timpson, Emma E. Vincent, Brian Keith, Ian A. Blair, Nicolas Skuli and M. Celeste Simon. https://cancerdiscovery.aacrjournals.org/content/11/12/3106
Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity – Rida Iftikhar, Harrison M. Penrose, Angelle N. King, Joshua S. Samudre, Morgan E. Collins, Alifiani B. Hartono, Sean B. Lee, Frank Lau, Melody Baddoo, Erik F. Flemington, Susan E. Crawford and Suzana D. Savkovic. https://www.nature.com/articles/s41389-021-00373-4

iRGD‐modified exosomes effectively deliver CPT1A siRNA to colon cancer cells, reversing oxaliplatin resistance by regulating fatty acid oxidation – Dan Lin, Haiyang Zhang, Rui Liu, Ting Deng, Tao Ning, Ming Bai, Yuchong Yang, Kegan Zhu, Junyi Wang, Jingjing Duan, Shaohua Ge, Bei Sun, Guoguang Ying, Yi Ba. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13052

Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway – Ming-Da Wang, Nan-Ya Wang, Hui-Lu Zhang, Li-Yang Sun, Qiu-Ran Xu, Lei Liang, Chao Li, Dong-Sheng Huang, Hong Zhu and Tian Yang. https://www.nature.com/articles/s41389-021-00364-5


Starvation


CARS senses cysteine deprivation to activate AMPK for cell survival – Mengqiu Yuan, Ronghui Yan, Yi Zhang, Yue Qiu, Zetan Jiang, Haiying Liu, Ying Wang, Linchong Sun, Huafeng Zhang, Ping Gao. https://www.embopress.org/doi/abs/10.15252/embj.2021108028
Autophagy is induced and modulated by cholesterol depletion through transcription of autophagy-related genes and attenuation of flux – Keren E. Shapira, Guy Shapira, Eran Schmukler, Metsada Pasmanik-Chor, Noam Shomron, Ronit Pinkas-Kramarski, Yoav I. Henis and Marcelo Ehrlich. https://www.nature.com/articles/s41420-021-00718-3

Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis – Maxime Uriarte, Nadine Sen Nkwe, Roch Tremblay, Oumaima Ahmed, Clémence Messmer, Nazar Mashtalir, Haithem Barbour, Louis Masclef, Marion Voide, Claire Viallard, Salima Daou, Djaileb Abdelhadi, Daryl Ronato, Mohammadjavad Paydar, Anaïs Darracq, Karine Boulay, Nicolas Desjardins-Lecavalier, Przemyslaw Sapieha, Jean-Yves Masson, Mikhail Sergeev, Benjamin H. Kwok, Laura Hulea, Frédérick A. Mallette, Eric Milot, Bruno Larrivée, Hugo Wurtele and El Bachir Affar. https://www.nature.com/articles/s41467-021-27306-4

Fasting-mimicking diet blocks triple-negative breast cancer and cancer stem cell escape – Giulia Salvadori, Federica Zanardi, Fabio Iannelli, Riccardo Lobefaro, Claudio Vernieri, Valter D. Longo. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00486-1


mTOR and nutrient sensing


The 40S-LARP1 complex reprograms the cellular translatome upon mTOR inhibition to preserve the protein synthetic capacity – Pedro Fuentes, Joffrey Pelletier, Carolina Martinez-Herráez, Virginia Diez-Obrero, Flavia Iannizzotto, Teresa Rubio, Marta Garcia-Cajide, Sandra Menoyo, Victor Moreno, Ramón Salazar, Albert Tauler, Antonio Gentilella. https://www.science.org/doi/full/10.1126/sciadv.abg9275
The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis – Motohiro Sekiya, Kenta Kainoh, Takehito Sugasawa, Ryunosuke Yoshino, Takatsugu Hirokawa, Hiroaki Tokiwa, Shogo Nakano, Satoru Nagatoishi, Kouhei Tsumoto, Yoshinori Takeuchi, Takafumi Miyamoto, Takashi Matsuzaka and Hitoshi Shimano. https://www.nature.com/articles/s41467-021-26638-5

AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake – Xi Sheng Rao, Xiao Xia Cong, Xiu Kui Gao, Yin Pu Shi, Lin Jing Shi, Jian Feng Wang, Chen-Yao Ni, Ming Jie He, Yingke Xu, Cong Yi, Zhuo-Xian Meng, Jinling Liu, Peng Lin, Li Ling Zheng and Yi Ting Zhou. https://www.nature.com/articles/s41418-021-00809-9


Glucose metabolism


Activation of the NRF2 antioxidant program sensitizes tumors to G6PD inhibition – Hongyu Ding, Zihong Chen , Katherine Wu, Shih Ming Huang, Warren L Wu, Sarah E LeBoeuf, Ray G Pillai , Joshua D Rabinowitz, Thales Papagiannakopoulos. https://www.science.org/doi/10.1126/sciadv.abk1023
Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets – Accalia Fu, Lara van Rooyen, Lindsay Evans, Nina Armstrong, Daina Avizonis, Tatsuya Kin, Gregory H. Bird, Anita Reddy, Edward T. Chouchani, Marc Liesa-Roig, Loren D. Walensky, A.M. James Shapiro, Nika N. Danial. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01519-9

Detection of glucose-derived D- and L-lactate in cancer cells by the use of a chiral NMR shift reagent – Eul Hyun Suh, Carlos F. G. C. Geraldes, Sara Chirayil, Brandon Faubert, Raul Ayala, Ralph J. DeBerardinis and A. Dean Sherry. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00267-4
Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2 – Tianshui Sun, Zhuonan Liu, Fangfang Bi, Qing Yang. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13076

GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain – Ghulam Hassan Dar, Cláudia C. Mendes, Wei-Li Kuan, Alfina A. Speciale, Mariana Conceição, André Görgens, Inna Uliyakina, Miguel J. Lobo, Wooi F. Lim, Samir EL Andaloussi, Imre Mäger, Thomas C. Roberts, Roger A. Barker, Deborah C. I. Goberdhan, Clive Wilson and Matthew J. A. Wood. https://www.nature.com/articles/s41467-021-27056-3

A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma – Corinne Beinat, Chirag B. Patel, Tom Haywood, Surya Murty, Lewis Naya, Jessa B. Castillo, Samantha T. Reyes, Megan Phillips, Pablo Buccino, Bin Shen, Jun Hyung Park, Mary Ellen I. Koran, Israt S. Alam, Michelle L. James, Dawn Holley, Kim Halbert, Harsh Gandhi, Joy Q. He, Monica Granucci, Eli Johnson, Daniel Dan Liu, Nobuko Uchida, Rahul Sinha, Pauline Chu, Donald E. Born, Geoffrey I. Warnock, Irving Weissman, Melanie Hayden-Gephart, Mehdi Khalighi, Tarik F. Massoud, Andrei Iagaru, Guido Davidzon, Reena Thomas, Seema Nagpal, Lawrence D. Recht and Sanjiv Sam Gambhir. https://clincancerres.aacrjournals.org/content/27/23/6467


Amino acids


The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases – Rossella Marullo, Monica Castro, Shira Yomtoubian, M. Nieves Calvo-Vidal, Maria Victoria Revuelta, Jan Krumsiek, Andrew Cho, Pablo Cresta Morgado, ShaoNing Yang, Vanina Medina, Berta M. Roth, Marcelo Bonomi, Kayvan R. Keshari, Vivek Mittal, Alfredo Navigante, Leandro Cerchietti. https://www.science.org/doi/full/10.1126/sciadv.abg1964

Expression and function of SLC38A5, an amino acid-coupled Na+/H+ exchanger, in triple-negative breast cancer and its relevance to macropinocytosis – Sabarish Ramachandran, Souad R. Sennoune, Monica Sharma, Muthusamy Thangaraju, Varshini V. Suresh, Tyler Sneigowski, Yangzom D. Bhutia, Kevin Pruitt, Vadivel Ganapathy. https://portlandpress.com/biochemj/article/478/21/3957/230003
Methionine synthase is essential for cancer cell proliferation in physiological folate environments – Mark R. Sullivan, Alicia M. Darnell, Montana F. Reilly, Tenzin Kunchok, Lena Joesch-Cohen, Daniel Rosenberg, Ahmed Ali, Matthew G. Rees, Jennifer A. Roth, Caroline A. Lewis and Matthew G. Vander Heiden. https://www.nature.com/articles/s42255-021-00486-5
Methionine synthase supports tumour tetrahydrofolate pools – Jonathan M. Ghergurovich, Xincheng Xu, Joshua Z. Wang, Lifeng Yang, Rolf-Peter Ryseck, Lin Wang and Joshua D. Rabinowitz. https://www.nature.com/articles/s42255-021-00465-w


Nucleotides and NAD


A novel oral inhibitor for one-carbon metabolism and checkpoint kinase 1 inhibitor as a rational combination treatment for breast cancer – Jin Lee, Xiaoxi Chen, Yuming Wang, Tatsunori Nishimura, Mengjiao Li, Satoko Ishikawa, Takiko Daikoku, Junya Kawai, Arinobu Tojo, Noriko Gotoh. https://www.sciencedirect.com/science/article/pii/S0006291X2101500X
Biguanide drugs enhance cytotoxic effects of cisplatin by depleting aspartate and NAD+ in sensitive cancer cells – Ellen Tully, Santosh Bharti, Juhyung Woo, Zaver Bhujwalla, Edward Gabrielson. https://www.tandfonline.com/doi/abs/10.1080/15384047.2021.1982599

LncRNA HIF1A-AS1 Promotes Gemcitabine Resistance of Pancreatic Cancer by Enhancing Glycolysis through Modulating the AKT/YB1/HIF1α Pathway – Fengyu Xu, Mengqi Huang, Qingyong Chen, Yi Niu, Yuhang Hu, Ping Hu, Ding Chen, Chi He, Kang Huang, Zhu Zeng, Jiang Tang, Fan Wang, Yong Zhao, Chunyou Wang and Gang Zhao. https://cancerres.aacrjournals.org/content/81/22/567
Hypoxia Drives Dihydropyrimidine Dehydrogenase Expression in Macrophages and Confers Chemoresistance in Colorectal Cancer – Marie Malier, Khaldoun Gharzeddine, Marie-Hélène Laverriere, Sabrina Marsili, Fabienne Thomas, Thomas Decaens, Gael Roth and Arnaud Millet. https://cancerres.aacrjournals.org/content/81/23/5963


Cancer Immunometabolism


Lactate supports a metabolic-epigenetic link in macrophage polarization – Jordan T. Noe, Beatriz E. Rendon, Anne E. Geller, Lindsey R. Conroy, Samantha M. Morrissey, Lyndsay E.A. Young, Ronald C. Bruntz, Eun J. Kim, Ashley Wise-Mitchell, Mariana Barbosa de Souza Rizzo, Eric R. Relich, Becca V. Baby, Lance A. Johnson, Hayley C. Affronti, Kelly M. McMasters, Brian F. Clem, Matthew S. Gentry, Jun Yan, Kathryn E. Wellen, Ramon C. Sun, Robert A. Mitchell. https://www.science.org/doi/full/10.1126/sciadv.abi8602

Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis – Maria I. Matias, Carmen S. Yong, Amir Foroushani, Chloe Goldsmith, Cédric Mongellaz, Erdinc Sezgin, Kandice R. Levental, Ali Talebi, Julie Perrault, Anais Rivière, Jonas Dehairs, Océane Delos, Justine Bertand-Michel, Jean-Charles Portais, Madeline Wong, Julien C. Marie, Ameeta Kelekar, Sandrina Kinet, Valérie S. Zimmermann, Ilya Levental, Laurent Yvan-Charvet, Johannes V. Swinnen, Stefan A. Muljo, Hector Hernandez-Vargas, Saverio Tardito, Naomi Taylor, Valérie Dardalhon. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01384-X
Manipulation of epithelial-to-mesenchymal transition reveals metastatic breast cancers support immune suppression via heme metabolism – Michelle Williams, Sabrina Hafeez, Jessica Christenson, Nicole Spoelstra, Jill Slansky and Jennifer Richer. https://jitc.bmj.com/content/9/Suppl_2/A933
Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma – Lijie Zhai, April Bell, Erik Ladomersky, Kristen L. Lauing, Lakshmi Bollu, Brenda Nguyen, Matthew Genet, Miri Kim, Peiwen Chen, Xinlei Mi, Jennifer D. Wu, Matthew J. Schipma, Brian Wray, John Griffiths, Richard D. Unwin, Simon J. Clark, Rajesh Acharya, Riyue Bao, Craig Horbinski, Rimas V. Lukas, Gary E. Schiltz and Derek A. Wainwright. https://clincancerres.aacrjournals.org/content/27/23/651


Reviews


Tumour fatty acid metabolism in the context of therapy resistance and obesity – Andrew J. Hoy, Shilpa R. Nagarajan and Lisa M. Butler. https://www.nature.com/articles/s41568-021-00388-4

Compartmentalization and metabolic regulation of glycolysis – Gregory G. Fuller, John K. Kim. https://journals.biologists.com/jcs/article-abstract/134/20/jcs258469/272535
Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited – Chenfeng Han, Minmin Ge, Ping-Chih Ho and Lianjun Zhang. https://cancerimmunolres.aacrjournals.org/content/early/2021/10/29/2326-6066.CIR-21-0459
The Neglected Liaison: Targeting Cancer Cell Metabolic Reprogramming Modifies the Composition of Non-Malignant Populations of the Tumor Microenvironment – Maria Iorio, Nikkitha Umesh Ganesh, Monica De Luise, Anna Maria Porcelli, Giuseppe Gasparre, Ivana Kurelac. https://www.mdpi.com/2072-6694/13/21/5447
Sirtuins as Metabolic Regulators of Immune Cells Phenotype and Function – Lídia Fortuny and Carlos Sebastián. https://www.mdpi.com/2073-4425/12/11/1698
The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions – Alexandre Vallée, Yves Lecarpentier, Jean-Noël Vallée. https://pubmed.ncbi.nlm.nih.gov/34771718/


Comments / other


Lipid metabolism: new twists to the Yin and Yang of PKM2 in cancer – Ali Khateb, Ze’ev A Ronai. https://www.embopress.org/doi/abs/10.15252/embj.2021109683
Mitochondria-More than just ATP for CTLs – Jonathan S. Maltzman. https://www.science.org/doi/full/10.1126/sciimmunol.eabn0249

Upcycling the TCA cycle—rewiring tumour-associated fibroblasts – Zachary A. Bacigalupa & W. Kimryn Rathmell. https://www.nature.com/articles/s42255-021-00473-w
A new foe in folate metabolism – Zhengwei Wu and Wai Leong Tam. https://www.nature.com/articles/s42255-021-00474-9
AMPK-activated ULK1 phosphorylates PIKFYVE to drive formation of PtdIns5P-containing autophagosomes during glucose starvation – Cansu Karabiyik and David C. Rubinsztein
https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1961409
AMPK CA(R)Sts a new light on amino acid sensing – Kristin K Brown. https://www.embopress.org/doi/abs/10.15252/embj.2021109575

Targeting glutamine metabolism and autophagy: the combination for prostate cancer radiosensitization – Anna Mukha, Uğur Kahya and Anna Dubrovska. https://www.tandfonline.com/doi/full/10.1080/15548627.2021.1962682

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