Search

Your search keyword '"Matthew J. P. Rush"' showing total 4 results
Start Over Author "Matthew J. P. Rush" Topic biology
4 results on '"Matthew J. P. Rush"'

1. Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling

Author

David J. Pagliarini, Mike T. Veling, Kyle J. Connors, Zachary A. Kemmerer, Arne Ulbrich, Alicia L. Richards, Jacob Sokol, Joshua J. Coon, Elyse C. Freiberger, Paul D. Hutchins, Xiao Guo, Michael S. Westphall, Harald Marx, Nicholas W. Kwiecien, Alexander S. Hebert, Jonathan A. Stefely, Kyle P. Robinson, Edna A. Trujillo, Matthew J. P. Rush, and Adam Jochem

Subjects
0301 basic medicine, Neurodegeneration, Biomedical Engineering, Bioengineering, Computational biology, Biology, Mitochondrion, medicine.disease, Proteomics, Applied Microbiology and Biotechnology, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Metabolomics, Coenzyme Q – cytochrome c reductase, Lipidomics, Proteome, medicine, Molecular Medicine, Gene, 030217 neurology & neurosurgery, Biotechnology
Abstract

Proteomics, lipidomics and metabolomics of single gene deletion yeast strains sheds light on mitochondrial protein biology. Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized. We present a multi-omic data analysis and visualization tool that we use to find covariance networks that can predict molecular functions, correlations between profiles of related gene deletions, gene-specific perturbations that reflect protein functions, and a global respiration deficiency response. Using this multi-omic approach, we link seven proteins including Hfd1p and its human homolog ALDH3A1 to mitochondrial coenzyme Q (CoQ) biosynthesis, an essential pathway disrupted in many human diseases. This Resource should provide molecular insights into mitochondrial protein functions.

Published
2016

2. Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys

Author

Sean J. McIlwain, Joshua J. Coon, Ricki J. Colman, Josef P. Clark, Paul D. Hutchins, Rozalyn M. Anderson, Hamid R. Eghbalnia, Maggie S. Burhans, Derek M. Pavelec, Jaime L. Stark, Irene M. Ong, John L. Markley, Vincent B. Chen, Timothy W. Rhoads, Matthew J. P. Rush, and John M. Denu

Subjects
0301 basic medicine, Male, Aging, Physiology, Gene Expression, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Metabolome, Animals, RNA Processing, Post-Transcriptional, Molecular Biology, Gene, Caloric Restriction, biology, Lipid metabolism, Cell Biology, Metabolism, biology.organism_classification, Macaca mulatta, Cell biology, Rhesus macaque, Metabolic pathway, 030104 developmental biology, Liver, RNA, 030217 neurology & neurosurgery, Drug metabolism
Abstract

Summary Caloric restriction (CR) extends lifespan and delays the onset of age-related disorders in diverse species. Metabolic regulatory pathways have been implicated in the mechanisms of CR, but the molecular details have not been elucidated. Here, we show that CR engages RNA processing of genes associated with a highly integrated reprogramming of hepatic metabolism. We conducted molecular profiling of liver biopsies collected from adult male rhesus monkeys ( Macaca mulatta ) at baseline and after 2 years on control or CR (30% restricted) diet. Quantitation of over 20,000 molecules from the hepatic transcriptome, proteome, and metabolome indicated that metabolism and RNA processing are major features of the response to CR. Predictive models identified lipid, branched-chain amino acid, and short-chain carbon metabolic pathways, with alternate transcript use for over half of the genes in the CR network. We conclude that RNA-based mechanisms are central to the CR response and integral in metabolic reprogramming.

Published
2017

3. Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity

Author

Catherine E. Minogue, David J. Pagliarini, Floriana Licitra, Anna Isabel Schlagowski, Danielle C. Lohman, Fabien Pierrel, Laurence Reutenauer, Isabel E. Johnson, Joffrey Zoll, Andrew G. Reidenbach, Natarajan Kannan, Pankaj Kumar Singh, Zachary A. Kemmerer, Xiao Guo, Emily M. Wilkerson, Alexander S. Hebert, Jonathan A. Stefely, Matteo Dal Peraro, Paul D. Hutchins, Zheng Ruan, Matthew J. P. Rush, Craig A. Bingman, Nicholas W. Kwiecien, Pavel J. Sindelar, Joshua J. Coon, Adam Jochem, Tiphaine Jaeg-Ehret, Brendan J. Floyd, Anais Grangeray, Arne Ulbrich, Michael S. Westphall, Hélène Puccio, Leila Laredj, Maya Chergova, Philippe Isope, Deniz Aydin, Elyse C. Freiberger, Ulrika Forsman, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Instituto de Quimica - Universidade Federal do Rio Grande do Sul, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Centre for Materials Research, UCL, University College of London [London] (UCL), Department of Chemistry, UCL, Christopher Ingold Laboratories, Central European University [Budapest, Hongrie] (CEU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génie et Microbiologie des Procédés Alimentaires (GMPA), National Engineering Research Center for Information Technology in Agriculture [Beijing] (NERCITA), Institute for Biomedicine of Aging, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC), Global Health Institute - Institut d'Infectiologie [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie des Processus Biologiques (LCPB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Engineering Science, University of Oxford [Oxford], Département Neurotransmission et sécrétion neuroendocrine, Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Central European University (CEU), Global Health Institute, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des Neurosciences Cellulaires et Intégratives (INCI)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), University of Oxford, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), AgroParisTech-Institut National de la Recherche Agronomique (INRA), and Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
0301 basic medicine, Male, Models, Molecular, Proteomics, Time Factors, Protein Conformation, Ubiquinone, Purkinje cell, 0302 clinical medicine, Cerebellum, Chlorocebus aethiops, Mice, Knockout, Exercise Tolerance, Behavior, Animal, Kinase, food and beverages, medicine.anatomical_structure, Phenotype, Biochemistry, COS Cells, Female, medicine.symptom, Protein Binding, Ataxia, Saccharomyces cerevisiae Proteins, Cerebellar Ataxia, Saccharomyces cerevisiae, Biology, Motor Activity, Transfection, Article, Mitochondrial Proteins, 03 medical and health sciences, Structure-Activity Relationship, Seizures, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetic Predisposition to Disease, Muscle Strength, Kinase activity, Protein kinase A, Maze Learning, Muscle, Skeletal, Molecular Biology, Cerebellar ataxia, HEK 293 cells, Recognition, Psychology, Cell Biology, Lipid Metabolism, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, HEK293 Cells, Rotarod Performance Test, 030217 neurology & neurosurgery, ADCK3
Abstract

International audience; The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.

Published
2016
Full Text
View/download PDF

4. Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q Production

Author

Adam Jochem, Joshua J. Coon, Mike T. Veling, Elyse C. Freiberger, Arne Ulbrich, Jason D. Russell, Matthew J. P. Rush, Michael J. Drahnak, Andrew G. Reidenbach, Nicholas W. Kwiecien, David J. Pagliarini, and Paul D. Hutchins

Subjects
Proteomics, 0301 basic medicine, Saccharomyces cerevisiae Proteins, Time Factors, Methyltransferase, Genotype, Ubiquinone, Saccharomyces cerevisiae, Computational biology, Aminopeptidases, Article, 03 medical and health sciences, Protein Domains, Enzyme Stability, Metabolomics, Molecular Biology, biology, Edman degradation, CoQ Deficiency, food and beverages, Methyltransferases, Cell Biology, biology.organism_classification, Mitochondrial respiration, Mitochondria, Phenotype, 030104 developmental biology, Biochemistry, Mitochondrial matrix, Coenzyme Q – cytochrome c reductase, Mutation, Energy Metabolism, Protein Processing, Post-Translational, Single mutation
Abstract

Mitoproteases are becoming recognized as key regulators oninef diverse mitochondrial functions, although their direct substrates are often difficult to discern. Through multi-omic profiling of diverse Saccharomyces cerevisiae mitoprotease deletion strains, we predicted numerous associations between mitoproteases and distinct mitochondrial processes. These include a strong association between the mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis—a pathway essential for mitochondrial respiration. Through Edman sequencing, and in vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the N-terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves its stability. A single mutation to the Oct1p recognition motif in Coq5p disrupted its processing in vivo, leading to CoQ deficiency and respiratory incompetence. This work defines the Oct1p processing of Coq5p as an essential post-translational event for proper CoQ production. Additionally, our data visualization tool enables efficient exploration of mitoprotease profiles that can serve as the basis for future mechanistic investigations.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results