Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth

PloS One
Esko KemppainenHoward T Jacobs

Abstract

The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level.

References

Oct 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·D R Cavener, R J MacIntyre
Jan 1, 1994·Methods in Cell Biology·A H BrandN Perrimon
Jan 20, 1998·Gene·Z H ShahH T Jacobs
Jul 25, 1998·Advances in Genetics·A Lambertsson
Jul 14, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S Roy, K VijayRaghavan
Oct 27, 2004·Annals of Neurology·Chaya MillerOrly Elpeleg
Dec 4, 2004·Biochimica Et Biophysica Acta·Howard T JacobsKevin M C O'Dell
Dec 29, 2004·Diabetes Research and Clinical Practice·Nessar Ahmed
Nov 29, 2005·Journal of Insect Physiology·Julian A T Dow, Shireen A Davies
May 2, 2006·Genetics·Tim FergestadBarry Ganetzky
Feb 5, 2008·Molecular Genetics and Metabolism·UNKNOWN Mitochondrial Medicine Society's Committee on DiagnosisRobert K Naviaux
Aug 22, 2009·Annual Review of Genetics·Ville Hietakangas, Stephen M Cohen
Oct 30, 2009·The Journal of Biological Chemistry·Tomoko SunamiSujata Sharma
Jan 13, 2010·PloS One·Daniel J M Fernández-AyalaHoward T Jacobs
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Feb 2, 2010·Nature Chemical Biology·Tilman Schneider-PoetschJun O Liu
Feb 20, 2010·Human Molecular Genetics·Sofia Ahola-ErkkiläAnu Suomalainen
Apr 17, 2010·Journal of Biomedicine & Biotechnology·Paulien SmitsLambert van den Heuvel
Jun 18, 2011·Molecular Biology of the Cell·Guillaume A CastillonManuel Muñiz
Jul 6, 2011·The Journal of Cell Biology·Morihisa FujitaTaroh Kinoshita
Oct 27, 2011·Journal of Diabetes Science and Technology·Stefano FerriKoji Sode
Dec 16, 2011·The Biochemical Journal·Brian MagnusonDiane C Fingar
Jan 31, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Douglas S Kerr
Aug 8, 2013·Molecular Genetics and Metabolism·Colleen ClarkeMarni J Falk
Sep 11, 2013·Annual Review of Genetics·Bruno Lemaitre, Irene Miguel-Aliaga
Sep 14, 2013·Mitochondrion·M AdevaC Donapetry

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Citations

Jun 18, 2017·Journal of Insect Physiology·Samuel G Towarnicki, J William O Ballard
Jun 21, 2019·Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology·Sina SaariHoward T Jacobs
May 12, 2019·G3 : Genes - Genomes - Genetics·Tiina S SalminenLaurie S Kaguni
Jan 12, 2020·Journal of Biochemistry·Howard T JacobsEsko Kemppainen
Jun 27, 2018·Integrative and Comparative Biology·Justin L BuchananKristi L Montooth
Nov 26, 2019·Wellcome Open Research·Karl J MortenJoanna Poulton
Apr 10, 2020·Frontiers in Immunology·Tiina S Salminen, Pedro F Vale
May 11, 2017·Scientific Reports·Tetsuo YasugiTakashi Nishimura
Jul 1, 2019·G3 : Genes - Genomes - Genetics·Tiina S SalminenLaurie S Kaguni

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Methods Mentioned

BETA
transgenic
enzyme-linked luminometry
RNAseq

Software Mentioned

TopHat
CuffDiff
QRTPCR

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