MetaboList – September 2021


Mitochondria


Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stress – Max-Hinderk Schuler, Alyssa M. English, Tianyao Xiao, Thane J. Campbell, Janet M. Shaw, Adam L. Hughes. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00688-2

NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation – Alexandros Papachristodoulou, Antonio Rodriguez-Calero, Sukanya Panja, Elizabeth Margolskee, Renu K. Virk, Teresa A. Milner, Luis Pina Martina, Jaime Y. Kim, Matteo Di Bernardo, Alanna B. Williams, Elvis A. Maliza, Joseph M. Caputo, Christopher Haas, Vinson Wang, Guarionex Joel De Castro, Sven Wenske, Hanina Hibshoosh, James M. McKiernan, Michael M. Shen, Mark A. Rubin, Antonina Mitrofanova, Aditya Dutta and Cory Abate-Shen. https://cancerdiscovery.aacrjournals.org/content/11/9/2316

Oxidative bursts of single mitochondria mediate retrograde signaling toward the ER – David M. Booth, Péter Várnai, Suresh K. Joseph, György Hajnóczky. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00583-9?dgcid=raven_jbs_etoc_email

PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells – Gabriele Bluemel, Mélanie Planque Corina T. Madreiter-Sokolowskide, Theresa Haitzmann, Andelko Hrzenjakaf, Wolfgang F.Graierdg ,Sarah-Maria Fendt, Horst Olschewskiaf, Katharina Leithner. https://www.sciencedirect.com/science/article/pii/S0891584921007206

EVT-701 is a novel selective and safe mitochondrial complex 1 inhibitor with potent anti-tumor activity in models of solid cancers – Raquel Luna Yolba, Virgile Visentin, Caroline Hervé  Johanna Chiche, Jean-Ehrland Ricci, Jérôme Méneyrol, Michaël R Paillasse, Nathalie Alet. https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.854

Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes – Clair Crewe, Jan-Bernd Funcke, Shujuan Li, Nolwenn Joffin, Christy M. Gliniak, Alexandra L. Ghaben, Yu A. An, Hesham A. Sadek, Ruth Gordillo, Yucel Akgul, Shiuhwei Chen, Dmitri Samovski, Pamela Fischer-Posovszky, Christine M. Kusminski, Samuel Klein, Philipp E. Scherer. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00365-X


PDH / TCA


Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion – Jana Škerlová, Jens Berndtsson, Hendrik Nolte, Martin Ott and Pål Stenmark. https://www.nature.com/articles/s41467-021-25570-y

The requirement for pyruvate dehydrogenase in leukemogenesis depends on cell lineage – Sojeong Jun, Swetha Mahesula, Thomas P. Mathews, Misty S. Martin-Sandoval, Zhiyu Zhao, Elena Piskounova, Michalis Agathocleous. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00332-6

Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer – Ritesh K Aggarwal, Rebecca A Luchtel, Venkata Machha, Alexander Tischer, Yiyu Zou, Kith Pradhan, Nadia Ashai, Nandini Ramachandra, Joseph M Albanese, Jung-In Yang, Xiaoyang Wang, Srinivas Aluri, Shanisha Gordon, Ahmed Aboumohamed, Benjamin A Gartrell, Sassan Hafizi, James Pullman, Niraj Shenoy. https://www.pnas.org/content/118/39/e2106947118.long

Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis – Yihong Huan, Shuo Zheng, Ying Lin and Liming Ke. https://journals.asm.org/doi/abs/10.1128/MCB.00609-20


Glucose metabolism


Hypoxia Promotes Breast Cancer Cell Growth by Activating a Glycogen Metabolic Program – Ke Tang, Liyan Zhu, Jie Chen, Dianheng Wang, Liping Zeng, Chen Chen, Liang Tang, Li Zhou, Keke Wei, Yabo Zhou, Jiadi Lv, Yuying Liu, Huafeng Zhang, Jingwei Ma and Bo Huang. https://cancerres.aacrjournals.org/content/81/19/4949

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia – Yusuke Saito, Mariko Kinoshita, Ai Yamada, Sayaka Kawano, Hong-Shan Liu, Sachiyo Kamimura, Midori Nakagawa, Syun Nagasawa, Tadao Taguchi, Shuhei Yamada, Hiroshi Moritake.. https://onlinelibrary.wiley.com/doi/10.1111/cas.15138

Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer – Kasey R. Cargill, C. Allison Stewart, Elizabeth M. Park, Kavya Ramkumar, Carl M. Gay, Robert J. Cardnell, Qi Wang, Lixia Diao, Li Shen, You-Hong Fan, Wai Kin Chan, Philip L. Lorenzi, Trudy G. Oliver, Jing Wang and Lauren A. Byers. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00270-9


Amino acid metabolism


Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells – Ibrahim H. Polat, Míriam Tarrado-Castellarnau, Adrian Benito, Claudia Hernandez-Carro, Josep Centelles, Silvia Marin and Marta Cascante. https://www.mdpi.com/2076-3921/10/9/1349

Metformin Is a Pyridoxal-5′-phosphate (PLP)-Competitive Inhibitor of SHMT2 – Angela Tramonti, Elisabet Cuyàs, José Antonio Encinar 5, Matthias Pietzke, Alessio Paone, Sara Verdura, Aina Arbusà  Begoña Martin-Castillo, Giorgio Giardina, Jorge Joven, Alexei Vazquez, Roberto Contestabile, Francesca Cutruzzolà, Javier A Menendez. https://www.mdpi.com/2072-6694/13/16/4009

ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restriction – Xingyao Li, Daniel Gracilla, Lun Cai, Mingyi Zhang, Xiaolin Yu, Xiaoguang Chen, Junran Zhang, Xiaochun Long, Han-Fei Ding, Chunhong Yan. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01153-0

MEF2D-NR4A1-FAM134B2-mediated reticulophagy contributes to amino acid homeostasis – Yuji Shiozaki, Shinobu Miyazaki-Anzai, Audrey L. Keenan and Makoto Miyazaki. https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1968228


Lipid metabolism/citrate


NaCT/SLC13A5 facilitates citrate import and metabolism under nutrient-limited conditions – Avi Kumar, Thekla Cordes, Anna E. Thalacker-Mercer, Ana M. Pajor, Anne N. Murphy, Christian M. Metallo. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01148-7

Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition – Lisa M. Butler, Chui Yan Mah, Jelle Machiels, Andrew D. Vincent, Swati Irani, Shadrack M. Mutuku, Xander Spotbeen, Muralidhararao Bagadi, David Waltregny, Max Moldovan, Jonas Dehairs, Frank Vanderhoydonc, Katarzyna Bloch, Rajdeep Das, Jurgen Stahl, James G. Kench, Thomas Gevaert, Rita Derua, Etienne Waelkens, Zeyad D. Nassar, Luke A. Selth, Paul J. Trim, Marten F. Snel, David J. Lynn, Wayne D. Tilley, Lisa G. Horvath, Margaret M. Centenera and Johannes V. Swinnen. https://cancerres.aacrjournals.org/content/81/19/4981


Nucleotides


A hydride transfer complex reprograms NAD metabolism and bypasses senescence – Sebastian Igelmann, Frédéric Lessard, Oro Uchenunu, Jacob Bouchard, Ana Fernandez-Ruiz, Marie-Camille Rowell, Stéphane Lopes-Paciencia, David Papadopoli, Aurélien Fouillen, Katia Julissa Ponce, Geneviève Huot, Lian Mignacca, Mehdi Benfdil, Paloma Kalegari, Haytham M. Wahba, Jan Pencik, Nhung Vuong, Jordan Quenneville, Jordan Guillon, Véronique Bourdeau, Laura Hulea, Etienne Gagnon, Lukas Kenner, Richard Moriggl, Antonio Nanci, Michael N. Pollak, James G. Omichinski, Ivan Topisirovic, Gerardo Ferbeyre. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00695-X

MTAP Deficiency–Induced Metabolic Reprogramming Creates a Vulnerability to Cotargeting De Novo Purine Synthesis and Glycolysis in Pancreatic Cancer – Qiangsheng Hu, Yi Qin, Shunrong Ji, Xiuhui Shi, Weixing Dai, Guixiong Fan, Shuo Li, Wenyan Xu, Wensheng Liu, Mengqi Liu, Zheng Zhang, Zeng Ye, Zhijun Zhou, Jingxuan Yang, Qifeng Zhuo, Xianjun Yu, Min Li and Xiaowu Xu. https://cancerres.aacrjournals.org/content/81/19/4964


AMPK


Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK – Che-Chia Hsu, Xian Zhang, Guihua Wang, Weina Zhang, Zhen Cai, Bo-Syong Pan, Haiwei Gu, Chuan Xu, Guoxiang Jin, Xiangshang Xu, Rajesh Kumar Manne, Yan Jin, Wei Yan, Jingwei Shao, Tingjin Chen, Emily Lin, Amit Ketkar, Robert Eoff, Zhi-Gang Xu, Zhong-Zhu Chen, Hong-Yu Li, Hui-Kuan Lin. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00692-4

AMPK-deficiency forces metformin-challenged cancer cells to switch from carbohydrate metabolism to ketogenesis to support energy metabolism – Flavio R. Palma, Bianca A. Ratti, Veronica Paviani, Diego R. Coelho, Rodrigo Miguel, Jeanne M. Danes, Sofia V. Zaichik, Andre L. de Abreu, Sueli O. Silva, Yiliang Chen, Roy L. Silverstein, Uppal Karan, Dean P. Jones and Marcelo G. Bonini. https://www.nature.com/articles/s41388-021-01943-x

Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy – Joshua C. Drake, Rebecca J. Wilson, Rhianna C. Laker, Yuntian Guan, Hannah R. Spaulding, Anna S. Nichenko, Wenqing Shen, Huayu Shang, Maya V. Dorn, Kian Huang, Mei Zhang, Aloka B. Bandara, Matthew H. Brisendine, Jennifer A. Kashatus, Poonam R. Sharma, Alexander Young, Jitendra Gautam, Ruofan Cao, Horst Wallrabe, Paul A. Chang, Michael Wong, Eric M. Desjardins, Simon A. Hawley, George J. Christ, David F. Kashatus, Clint L. Miller, Matthew J. Wolf, Ammasi Periasamy, Gregory R. Steinberg, D. Grahame Hardie, and Zhen Yan. https://www.pnas.org/content/118/37/e2025932118.abstract?etoc

Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function – Xiang Xu, Guangjin Ding, Caizhi Liu, Yuhan Ding, Xiaoxin Chen, Xiaoli Huang, Chen-Song Zhang, Shanxin Lu, Yunpeng Zhang, Yuanyong Huang, Zhaosu Chen, Wei Wei, Lujian Liao, Shu-Hai Lin, Jingya Li, Wei Liu, Jiwen Li, Sheng-Cai Lin, Xinran Ma, Jiemin Wong. https://doi.org/10.1038/s41422-021-00565-y


mTOR


Dissecting the biology of mTORC1 beyond rapamycin – Guang Yang, Deanne Francis, James R. Krycer, Mark Larance, Ziyang Zhang, Chris J. Novotny, Alexis Diaz-Vegas, Kevan M. Shokat, David E. James. https://www.science.org/doi/abs/10.1126/scisignal.abe0161

Amino acids and mechanistic target of rapamycin regulate the fate of live engulfed cells – Sung Eun Kim, Justin Zhang, Enoch Jiang, Michael Overholtzer. https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202100870R


IDH


Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells – Dong Chen, Siyuan Xia, Rukang Zhang, Yuancheng Li, Christopher A. Famulare, Hao Fan, Rong Wu, Mei Wang, Allen C. Zhu, Shannon E. Elf, Rui Su, Lei Dong, Martha Arellano, William G. Blum, Hui Mao, Sagar Lonial, Wendy Stock, Olatoyosi Odenike, Michelle Le Beau, Titus J. Boggon, Chuan He, Jianjun Chen, Xue Gao, Ross L. Levine, Jing Chen. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00507-4

Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis – Xun Liu, Kiyoshi Yamaguchi, Kiyoko Takane, Chi Zhu, Makoto Hirata, Yoko Hikiba, Shin Maeda, Yoichi Furukawa, Tsuneo Ikenoue. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257090

Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer – Shuang Qiao, Wenhua Lu, Christophe Glorieux, Jiangjiang Li, Peiting Zeng, Ning Meng, Huiqin Zhang, Shijun Wen and Peng Huang. https://www.nature.com/articles/s41388-021-01968-2

Mutant Idh2 Cooperates with a NUP98-HOXD13 Fusion to Induce Early Immature Thymocyte Precursor ALL – Liat Goldberg, Vijay Negi, Yang Jo Chung, Masahiro Onozawa, Yuelin J. Zhu, Robert L. Walker, Rachel Pierce, Daxesh P. Patel, Kristopher W. Krausz, Frank J. Gonzalez, Margaret A. Goodell, Benjamin A.T. Rodriguez, Paul S. Meltzer and Peter D. Aplan. https://cancerres.aacrjournals.org/content/81/19/5033

G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy – Mahmoud S. Alghamri, Brandon L. McClellan, Ruthvik P. Avvari, Rohit Thalla, Stephen Carney, Margaret S. Hartlage, Santiago Haase, Maria Ventosa, Ayman Taher, Neha Kamran, Li Zhang, Syed Mohd Faisal, Felipe J. Núñez, María Belén Garcia-Fabiani, Wajd N. Al-Holou, Daniel Orringer, Shawn Hervey-Jumper, Jason Heth, Parag G. Patil, Karen Eddy, Sofia D. Merajver, Peter J. Ulintz, Joshua Welch, Chao Gao, Jialin Liu, Gabriel Núñez, Dolores Hambardzumyan, Pedro R. Lowenstein, Maria G. Castro. https://www.science.org/doi/full/10.1126/sciadv.abh3243


Cancer Immunometabolism


G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy – Mahmoud S. Alghamri, Brandon L. McClellan, Ruthvik P. Avvari, Rohit Thalla, Stephen Carney, Margaret S. Hartlage, Santiago Haase, Maria Ventosa, Ayman Taher, Neha Kamran, Li Zhang, Syed Mohd Faisal, Felipe J. Núñez, María Belén Garcia-Fabiani, Wajd N. Al-Holou, Daniel Orringer, Shawn Hervey-Jumper, Jason Heth, Parag G. Patil, Karen Eddy, Sofia D. Merajver, Peter J. Ulintz, Joshua Welch, Chao Gao, Jialin Liu, Gabriel Núñez, Dolores Hambardzumyan, Pedro R. Lowenstein, Maria G. Castro. https://www.science.org/doi/full/10.1126/sciadv.abh3243

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation – Guillaume Bidault, Samuel Virtue, Kasparas Petkevicius, Helen E. Jolin, Aurélien Dugourd, Anne-Claire Guénantin, Jennifer Leggat, Betania Mahler-Araujo, Brian Y. H. Lam, Marcella K. Ma, Martin Dale, Stefania Carobbio, Arthur Kaser, Padraic G. Fallon, Julio Saez-Rodriguez, Andrew N. J. McKenzie and Antonio Vidal-Puig. https://www.nature.com/articles/s42255-021-00440-5


Miscellaneous


Brief report: The uricase mutation in humans increases our risk for cancer growth – Mehdi A. Fini, Miguel A. Lanaspa, Eric A. Gaucher, Brian Boutwell, Takahiko Nakagawa, Richard M. Wright, Laura G. Sanchez-Lozada, Peter Andrews, Kurt R. Stenmark and Richard J. Johnson. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00268-3

RB/E2F1 as a Master Regulator of Cancer Cell Metabolism in Advanced Disease – Amy C. Mandigo, Wei Yuan, Kexin Xu, Peter Gallagher, Angel Pang, Yi Fang Guan, Ayesha A. Shafi, Chellappagounder Thangavel, Beshara Sheehan, Denisa Bogdan, Alec Paschalis, Jennifer J. McCann, Talya S. Laufer, Nicolas Gordon, Irina A. Vasilevskaya, Emanuela Dylgjeri, Saswati N. Chand, Matthew J. Schiewer, Josep Domingo-Domenech, Robert B. Den, Jeff Holst, Peter A. McCue, Johann S. de Bono, Christopher McNair and Karen E. Knudsen. https://cancerdiscovery.aacrjournals.org/content/11/9/2334

Host autophagy mediates organ wasting and nutrient mobilization for tumor growth – Rojyar Khezri, Petter Holland, Todd Andrew Schoborg, Ifat Abramovich, Szabolcs Takáts, Caroline Dillard, Ashish Jain, Fergal O’Farrell, Sebastian Wolfgang Schultz, William M Hagopian, Eduardo Martin Quintana, Rachel Ng, Nadja Sandra Katheder, Mohammed Mahidur Rahman, José Gerardo Teles Reis, Andreas Brech, Heinrich Jasper, Nasser M Rusan, Anne Hope Jahren, Eyal Gottlieb, Tor Erik Rusten. https://www.embopress.org/doi/full/10.15252/embj.2020107336

Stable isotope tracing to assess tumor metabolism in vivo – Brandon Faubert, Alpaslan Tasdogan, Sean J. Morrison, Thomas P. Mathews and Ralph J. DeBerardinis. https://www.nature.com/articles/s41596-021-00605-2


Reviews


SnapShot: Cancer metabolism – Julia S. Brunner, Lydia W.S. Finley. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00501-3

Metabolic regulation of T cells in the tumor microenvironment by nutrient availability and diet – Steven Zhao, Ronal M. Peralta; Natalia Avina-Ochoa, Greg M. Delgoffe, Susan M.Kaech. https://www.sciencedirect.com/science/article/abs/pii/S1044532321000166?

AMPK: restoring metabolic homeostasis over space and time – Elijah Trefts, Reuben J. Shaw. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00682-1

Redox metabolism: ROS as specific molecular regulators of cell signaling and function – Claudia Lennicke, Helena M. Cochemé. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00685-7

Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity – Haejin Yoon, Jillian L. Shaw, Marcia C. Haigis, Anna Greka. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00694-8

Supply and demand: Cellular nutrient uptake and exchange in cancer – Vasileios Papalazarou, Oliver D.K. Maddocks. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00693-6

The context-specific roles of urea cycle enzymes in tumorigenesis – Emma Hajaj, Marco Sciacovelli, Christian Frezza, Ayelet Erez. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00645-6

Moonlighting functions of metabolic enzymes and metabolites in cancer – Chaoyun Pan, Bo Li, M. Celeste Simon. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00698-5

Metabolic channeling: predictions, deductions, and evidence – Vidhi Pareek, Zhou Sha, Jingxuan He, Ned S. Wingreen, Stephen J. Benkovic. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00697-3

The multifaceted regulation of mitophagy by endogenous metabolites – Ting Zhang, Qian Liu, Weihua Gao, Sheikh Arslan Sehgal and Hao Wu. https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1975914

The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance – Kangchen Chen, Chenzhi Zhang, Sunbin Ling, Rongli Wei, Jianguo Wang and Xiao Xu. https://www.nature.com/articles/s41419-021-04116-6


Comments


Cancer Signaling Drives Cancer Metabolism: AKT and the Warburg Effect – Aaron M. Hosios, and Brendan D. Manning. https://cancerres.aacrjournals.org/content/81/19/4896

More Metabolism! – James A. Olzmann, Sarah-Maria Fendt, Yatrik Shah, Karen Vousden, Navdeep Chandel, Tiffany Horng, Nika Danial, Benjamin Tu, Heather Christofk, Matthew G. Vander Heiden, Kathryn Wellen. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00712-7

Mitochondrial-derived compartments: A “fusel alcohol generator” in yeast? – Tim König, Heidi M. McBride. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00712-7

A novel redox cycle diverts cells from oncogene-induced senescence into cancer – Mate Maus, Manuel Serrano. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00690-0

Fatty Acid Synthesis in Prostate Cancer: Vulnerability or Epiphenomenon? – Laura A. Sena, and Samuel R. Denmeade. https://cancerres.aacrjournals.org/content/81/17/4385

T cells critically depend on pyruvate oxidation – Christopher Schrecker, Andrew M. Intlekofer. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00373-9


Online registrations available: EMBO workshop on Cancer Immunometabolism

https://meetings.embo.org/event/21-cancer

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