title: Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.
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.
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.
authors.forename: Esko
authors.initials: E
authors.lastname: Kemppainen
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.
authors.forename: Jack
authors.initials: J
authors.lastname: George
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.|Department of Molecular Biology and Genetics, Koç University, Sariyer, Istanbul, 34450, Turkey.
authors.forename: Görkem
authors.initials: G
authors.lastname: Garipler
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.
authors.forename: Tea
authors.initials: T
authors.lastname: Tuomela
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.
authors.forename: Essi
authors.initials: E
authors.lastname: Kiviranta
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, 997-0035, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sariyer, Istanbul, 34450, Turkey.
authors.forename: Cory D
authors.initials: CD
authors.lastname: Dunn
authors.affiliation: BioMediTech and Tampere University Hospital, FI-33014, University of Tampere, Tampere, Finland.|Institute of Biotechnology, FI-00014, University of Helsinki, Helsinki, Finland.
authors.forename: Howard T
authors.initials: HT
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D004032:Diet; D019422:Dietary Sucrose / Q000378:metabolism*; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D005260:Female; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D019422:Dietary Sucrose; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D019289:Pyruvic Acid
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