Mitochondrial dysfunction plus high-sugar diet provokes a metabolic crisis that inhibits growth

Esko Kemppainen, Jack George, Görkem Garipler, Tea Tuomela, Essi Kiviranta, Tomoyoshi Soga, Cory D. Dunn, Howard T. Jacobs

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The Drosophila mutant tko25t exhibits a deficiency ofmitochondrial 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 bymechanical 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.

Original languageEnglish
Article numbere0145836
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

ASJC Scopus subject areas

  • General

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