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Fly (Austin). 2019 Mar - Dec;13(1-4):12-28. doi: 10.1080/19336934.2019.1662266. Epub 2019 Sep 17.

Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae.

Author information

1
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
2
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Abstract

The Drosophila bang-sensitive mutant tko25t, manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko25t larvae, including elevated pyruvate and lactate, and found the larval gut to be a crucial tissue for the regulation of larval growth in the mutant. Here we established that expression of wild-type tko in any of several other tissues of tko25t also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko25t, producing developmental delay and bang-sensitivity. These findings imply the existence of a systemic signal regulating growth in response to mitochondrial dysfunction. Drugs and RNAi-targeted on pyruvate metabolism interacted with tko25t in ways that implicated pyruvate or one of its metabolic derivatives in playing a central role in generating such a signal. RNA-seq revealed that dietary pyruvate-induced changes in transcript representation were mostly non-coherent with those produced by tko25t or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level.

KEYWORDS:

Mitochondria; lactic acidosis; larva; protein synthesis; respiration; translation

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