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Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex I.
Zoe A Stephenson, Robert F Harvey, Kenneth R Pryde, Sarah Mistry, Rachel E Hardy, Riccardo Serreli, Injae Chung, Timothy EH Allen, Mark Stoneley, Marion MacFarlane, Peter M Fischer, Judy Hirst, Barrie Kellam, Anne E Willis
Jun 04, 2020
Biochemistry cancer biology cardiac liability chemical biology human Mitochondria toxicophore Adenosine Triphosphate Antineoplastic Agents Cell Death Cell Line Cell Proliferation Electron Transport Complex I Gene Expression Regulation Humans Mitochondria Mitochondria Heart Myocytes Cardiac Oxazoles Oxidative Phosphorylation Protein Binding Receptor ErbB-2 Triazoles
Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.
Marisa W Friederich, Sharita Timal, Christopher A Powell, Cristina Dallabona, Alina Kurolap, Sara Palacios-Zambrano, Drago Bratkovic, Terry GJ Derks, David Bick, Katelijne Bouman, Kathryn C Chatfield, Nadine Damouny-Naoum, Megan K Dishop, Tzipora C Falik-Zaccai, Fuad Fares, Ayalla Fedida, Ileana Ferrero, Renata C Gallagher, Rafael Garesse, Micol Gilberti, Cristina González, Katherine Gowan, Clair Habib, Rebecca K Halligan, Limor Kalfon, Kaz Knight, Dirk Lefeber, Laura Mamblona, Hanna Mandel, Adi Mory, John Ottoson, Tamar Paperna, Ger JM Pruijn, Pedro F Rebelo-Guiomar, Ann Saada, Bruno Sainz, Hayley Salvemini, Mirthe H Schoots, Jan A Smeitink, Maciej J Szukszto, Hendrik J Ter Horst, Frans van den Brandt, Francjan J van Spronsen, Joris A Veltman, Eric Wartchow, Liesbeth T Wintjes, Yaniv Zohar, Miguel A Fernández-Moreno, Hagit N Baris, Claudia Donnini, Michal Minczuk, Richard J Rodenburg, Johan LK Van Hove
Dec 07, 2018
Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a...
Amino Acid Sequence Cardiomyopathies Female FIBROBLASTS Humans Infant Infant Newborn Lentivirus Male Mitochondrial Diseases Models Molecular Mutation Myocardium Nitrogenous Group Transferases Oxidative Phosphorylation Pedigree Protein Biosynthesis Protein Subunits RNA Transfer Saccharomyces cerevisiae
The role of tRNA synthetases in neurological and neuromuscular disorders.
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNAs with their cognate amino acids, therefore essential for the first step in protein synthesis. Although the majority of protein...
lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.
M Joaquina Delás, Benjamin T Jackson, Tatjana Kovacevic, Silvia Vangelisti, Ester Munera Maravilla, Sophia A Wild, Eva Maria Stork, Nicolas Erard, Simon RV Knott, Gregory J Hannon
Apr 05, 2019
HSC Hematopoiesis lncRNA Oxidative Phosphorylation Animals Bone Marrow Transplantation Cell Differentiation Cell Line Tumor Cell Lineage Cyclin-Dependent Kinase 6 Female GATA2 Transcription Factor Hematopoiesis Hematopoietic Stem Cells Mice Mice Inbred C57BL Oxidative Phosphorylation Proto-Oncogene Proteins RNA Interference RNA Long Noncoding RNA Small Interfering Regeneration Trans-Activators
Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation.
Daniel J Fazakerley, Annabel Y Minard, James R Krycer, Kristen C Thomas, Jacqueline Stöckli, Dylan J Harney, James G Burchfield, Ghassan J Maghzal, Stuart T Caldwell, Richard C Hartley, Roland Stocker, Michael P Murphy, David E James
Jun 28, 2018
Mitochondrial oxidative stress, mitochondrial dysfunction, or both have been implicated in insulin resistance. However, disentangling the individual roles of these processes in insulin resistance has been difficult because they...
MITOCHONDRIAL DYSFUNCTION adipocyte Adipose Tissue Hydrogen Peroxide Insulin Insulin Resistance Mitochondria Muscle Oxidative Stress superoxide ion 3T3-L1 Cells Adenylate Kinase Adipocytes Animals Electron Transport Glucose Glucose Transporter Type 4 Herbicides Hydrogen Peroxide Insulin Insulin Resistance Male Mice Mice Inbred C57BL Mitochondria Myoblasts Oxidative Phosphorylation Oxygen Consumption Paraquat Peroxiredoxins Protein Isoforms Superoxides
Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts.
Craig Stamp, Anze Zupanic, Ashwin Sachdeva, Elizabeth A Stoll, Daryl P Shanley, John C Mathers, Thomas BL Kirkwood, Rakesh Heer, Benjamin D Simons, Doug M Turnbull, Laura C Greaves
Aug 09, 2018
Metabolic synthetic lethality in cancer therapy
Antimetabolites Antineoplastic Computer Simulation Energy Metabolism Forecasting Gene Dosage Gene Silencing Genes Neoplasm Humans Metabolome Mitochondria Mitochondrial Proteins Models Biological Molecular Targeted Therapy Neoplasm Proteins Neoplasms Oncogenes Oxidative Phosphorylation RNA Interference Synthetic Lethal Mutations
METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis.
Lindsey Van Haute, Alan G Hendrick, Aaron R D'Souza, Christopher A Powell, Pedro Rebelo-Guiomar, Michael E Harbour, ShuJing Ding, Ian M Fearnley, Byron Andrews, Michal Minczuk
Nov 26, 2019
Development and thyroid hormone dependence of skeletal muscle mitochondrial function towards birth.
Mitochondrial matrix-localized Src kinase regulates mitochondrial morphology.
Olivier Lurette, Hala Guedouari, Jordan L Morris, Rebeca Martín-Jiménez, Julie-Pier Robichaud, Geneviève Hamel-Côté, Mehtab Khan, Nicholas Dauphinee, Nicolas Pichaud, Julien Prudent, Etienne Hebert-Chatelain
Jun 07, 2022
The architecture of mitochondria adapts to physiological contexts: while mitochondrial fragmentation is usually associated to quality control and cell death, mitochondrial elongation often enhances cell survival during stress....
The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours
Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions.
Mitochondria are ubiquitous intracellular organelles found in almost all eukaryotes and involved in various aspects of cellular life, with a primary role in energy production. The interest in this organelle has grown stronger...
Genome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia.
Luke W Thomas, Cinzia Esposito, Rachel E Morgan, Stacey Price, Jamie Young, Steven P Williams, Lucas A Maddalena, Ultan McDermott, Margaret Ashcroft
Apr 07, 2021
An inhibitor of oxidative phosphorylation exploits cancer vulnerability.
Jennifer R Molina, Yuting Sun, Marina Protopopova, Sonal Gera, Madhavi Bandi, Christopher Bristow, Timothy McAfoos, Pietro Morlacchi, Jeffrey Ackroyd, Ahmed-Noor A Agip, Gheath Al-Atrash, John Asara, Jennifer Bardenhagen, Caroline C Carrillo, Christopher Carroll, Edward Chang, Stefan Ciurea, Jason B Cross, Barbara Czako, Angela Deem, Naval Daver, John Frederick de Groot, Jian-Wen Dong, Ningping Feng, Guang Gao, Jason Gay, Mary Geck Do, Jennifer Greer, Virginia Giuliani, Jing Han, Lina Han, Verlene K Henry, Judy Hirst, Sha Huang, Yongying Jiang, Zhijun Kang, Tin Khor, Sergej Konoplev, Yu-Hsi Lin, Gang Liu, Alessia Lodi, Timothy Lofton, Helen Ma, Mikhila Mahendra, Polina Matre, Robert Mullinax, Michael Peoples, Alessia Petrocchi, Jaime Rodriguez-Canale, Riccardo Serreli, Thomas Shi, Melinda Smith, Yoko Tabe, Jay Theroff, Stefano Tiziani, Quanyun Xu, Qi Zhang, Florian Muller, Ronald A DePinho, Carlo Toniatti, Giulio F Draetta, Timothy P Heffernan, Marina Konopleva, Philip Jones, M Emilia Di Francesco, Joseph R Marszalek
Jun 21, 2018
Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging...
Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.
Evanna L Mills, Beth Kelly, Angela Logan, Ana SH Costa, Mukund Varma, Clare E Bryant, Panagiotis Tourlomousis, J Henry M Däbritz, Eyal Gottlieb, Isabel Latorre, Sinéad C Corr, Gavin McManus, Dylan Ryan, Howard T Jacobs, Marten Szibor, Ramnik J Xavier, Thomas Braun, Christian Frezza, Michael P Murphy, Luke A O'Neill
Nov 22, 2017
Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation...
immunometabolism innate immunity macrophage reverse electron transport Succinate Succinate Dehydrogenase Toll-Like Receptors Adenosine Triphosphate Animals Carbonyl Cyanide m-Chlorophenyl Hydrazone Citric Acid Cycle Glycolysis Hypoxia-Inducible Factor 1 alpha Subunit Inflammation Interleukin-10 Lipopolysaccharides Macrophage Activation MACROPHAGES Malonates Membrane potential Mitochondrial Mice Mice Inbred C57BL Mitochondria Mitochondrial Proteins Oxidation-Reduction Oxidative Phosphorylation Oxidoreductases Plant Proteins Reactive Oxygen Species Sequence Analysis RNA Succinate Dehydrogenase Succinic Acid Transcriptome
Metabolic basis to Sherpa altitude adaptation.
James A Horscroft, Aleksandra O Kotwica, Verena Laner, James A West, Philip J Hennis, Denny ZH Levett, David J Howard, Bernadette O Fernandez, Sarah L Burgess, Zsuzsanna Ament, Edward T Gilbert-Kawai, André Vercueil, Blaine D Landis, Kay Mitchell, Monty G Mythen, Cristina Branco, Randall S Johnson, Martin Feelisch, Hugh E Montgomery, Julian L Griffin, Michael PW Grocott, Erich Gnaiger, Daniel S Martin, Andrew J Murray
May 16, 2017
Altitude Hypoxia metabolism Mitochondria Skeletal muscle Adaptation Physiological Adult Altitude Atmospheric Pressure Citric Acid Cycle Energy Metabolism Ethnicity Fatty Acids Female Gene Frequency Glucose Glycolysis Humans Hypoxia Male Mitochondria Muscle Muscle Skeletal Nepal Nitric oxide Oxidative Phosphorylation Oxidative Stress Oxygen Consumption PPAR alpha Polymorphism Single Nucleotide Tibet
Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia.
Veronika Ecker, Martina Stumpf, Lisa Brandmeier, Tanja Neumayer, Lisa Pfeuffer, Thomas Engleitner, Ingo Ringshausen, Nina Nelson, Manfred Jücker, Stefan Wanninger, Thorsten Zenz, Clemens Wendtner, Katrin Manske, Katja Steiger, Roland Rad, Markus Müschen, Jürgen Ruland, Maike Buchner
Jul 28, 2021
Current therapeutic approaches for chronic lymphocytic leukemia (CLL) focus on the suppression of oncogenic kinase signaling. Here, we test the hypothesis that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT...
Cell Line Tumor Mitochondria Animals Mice Transgenic Humans Mice Disease Progression Reactive Oxygen Species RNA Small Interfering Transplantation Homologous Immunohistochemistry Xenograft Model Antitumor Assays Signal Transduction Cell Death Cell Survival Oxidative Phosphorylation Proto-Oncogene Proteins c-akt Leukemia Lymphocytic Chronic B-Cell Phosphatidylinositol 3-Kinases Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases RNA-seq
Published by: Nature Communications
Mitochondrial matrix-localized Src kinase regulates mitochondrial morphology
Olivier Lurette, Hala Guedouari, Jordan L. Morris, Rebeca Martín-Jiménez, Julie-Pier Robichaud, Geneviève Hamel-Côté, Mehtab Khan, Nicholas Dauphinee, Nicolas Pichaud, Julien Prudent, Etienne Hebert-Chatelain
Jun 29, 2022
Abstract: The architecture of mitochondria adapts to physiological contexts: while mitochondrial fragmentation is usually associated to quality control and cell death, mitochondrial elongation often enhances cell survival during...
Macrophage innate training induced by IL-4 and IL-13 activation enhances OXPHOS driven anti-mycobacterial responses.
Mimmi LE Lundahl, Morgane Mitermite, Dylan Gerard Ryan, Sarah Case, Niamh C Williams, Ming Yang, Roisin I Lynch, Eimear Lagan, Filipa M Lebre, Aoife L Gorman, Bojan Stojkovic, Adrian P Bracken, Christian Frezza, Frederick J Sheedy, Eoin M Scanlan, Luke AJ O'Neill, Stephen V Gordon, Ed C Lavelle
Oct 29, 2022
Spatial mapping of mitochondrial networks and bioenergetics in lung cancer.
Mingqi Han, Eric A Bushong, Mayuko Segawa, Alexandre Tiard, Alex Wong, Morgan R Brady, Milica Momcilovic, Dane M Wolf, Ralph Zhang, Anton Petcherski, Matthew Madany, Shili Xu, Jason T Lee, Masha V Poyurovsky, Kellen Olszewski, Travis Holloway, Adrian Gomez, Maie St John, Steven M Dubinett, Carla M Koehler, Orian S Shirihai, Linsey Stiles, Aaron Lisberg, Stefano Soatto, Saman Sadeghi, Mark H Ellisman, David B Shackelford
Apr 03, 2023
Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation
Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8+ and CD4+...
Published by: Rockefeller University
Mitochondrial Transcription and Translation
Mitochondria are the major source of ATP in the cell. Five multi-subunit complexes in the inner membrane of the organelle are involved in the oxidative phosphorylation required for ATP production. Thirteen subunits of these...
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