Drosophila clueless is highly expressed in larval neuroblasts, affects mitochondrial localization and suppresses mitochondrial oxidative damage

Mitochondria are critical for neuronal function due to the high demand of ATP in these cell types. During Drosophila development, neuroblasts in the larval brain divide asymmetrically to populate the adult central nervous system. While many of the proteins responsible for maintaining neuroblast cell...

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Published in:	PloS one Vol. 8; no. 1; p. e54283
Main Authors:	Sen, Aditya, Damm, Vanessa T, Cox, Rachel T
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 16-01-2013 Public Library of Science (PLoS)
Subjects:	Adults Animals Animals, Genetically Modified ATP BASIC BIOLOGICAL SCIENCES Biochemistry Biology Brain Cell cycle cell cycle and cell division Cell division Cell fate Central nervous system Coordination Cytology cytoplasm Damage localization Defects Division Drosophila Drosophila melanogaster Drosophila Proteins - genetics Drosophila Proteins - metabolism Electron transport Gene expression Genomes Genomics germ cells Glycolysis Insects Larva Larvae Larval development Localization Metabolism Mitochondria Mitochondria - metabolism Molecular biology Muscles Mutants Mutation Nervous system Neuroblasts Neurons Neurophysiology Neurosciences Nuclear Proteins - genetics Nuclear Proteins - metabolism oxidative damage Oxidative Phosphorylation Oxidative stress Phosphorylation Physiological aspects Proteins United States > US Maryland
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Summary:	Mitochondria are critical for neuronal function due to the high demand of ATP in these cell types. During Drosophila development, neuroblasts in the larval brain divide asymmetrically to populate the adult central nervous system. While many of the proteins responsible for maintaining neuroblast cell fate and asymmetric cell divisions are known, little is know about the role of metabolism and mitochondria in neuroblast division and maintenance. The gene clueless (clu) has been previously shown to be important for mitochondrial function. clu mutant adults have severely shortened lifespans and are highly uncoordinated. Part of their lack of coordination is due to defects in muscle, however, in this study we have identified high levels of Clu expression in larval neuroblasts and other regions of the dividing larval brain. We show while mitochondria in clu mutant neuroblasts are mislocalized during the cell cycle, surprisingly, overall brain morphology appears to be normal. This is explained by our observation that clu mutant larvae have normal levels of ATP and do not suffer oxidative damage, in sharp contrast to clu mutant adults. Mutations in two other genes encoding mitochondrial proteins, technical knockout and stress sensitive B, do not cause neuroblast mitochondrial mislocalization, even though technical knockout mutant larvae suffer oxidative damage. These results suggest Clu functions upstream of electron transport and oxidative phosphorylation, has a role in suppressing oxidative damage in the cell, and that lack of Clu's specific function causes mitochondria to mislocalize. These results also support the previous observation that larval development relies on aerobic glycolysis, rather than oxidative phosphorylation. Thus Clu's role in mitochondrial function is not critical during larval development, but is important for pupae and adults.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Center for Neuroscience and Regeneration CO71IQ; G171JA Uniformed Services University of the Health Sciences (USUHS) Conceived and designed the experiments: AS RTC. Performed the experiments: AS VTD RTC. Analyzed the data: AS VTD RTC. Wrote the paper: RTC. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0054283