Abstract
BackgroundMammalian ATAD3 is a mitochondrial protein, which is thought to play an important role in nucleoid organization. However, its exact function is still unresolved.ResultsHere, we characterize the Caenorhabditis elegans (C. elegans) ATAD3 homologue (ATAD-3) and investigate its importance for mitochondrial function and development. We show that ATAD-3 is highly conserved among different species and RNA mediated interference against atad-3 causes severe defects, characterized by early larval arrest, gonadal dysfunction and embryonic lethality. Investigation of mitochondrial physiology revealed a disturbance in organellar structure while biogenesis and function, as indicated by complex I and citrate synthase activities, appeared to be unaltered according to the developmental stage. Nevertheless, we observed very low complex I and citrate synthase activities in L1 larvae populations in comparison to higher larval and adult stages. Our findings indicate that atad-3(RNAi) animals arrest at developmental stages with low mitochondrial activity. In addition, a reduced intestinal fat storage and low lysosomal content after depletion of ATAD-3 suggests a central role of this protein for metabolic activity.ConclusionsIn summary, our data clearly indicate that ATAD-3 is essential for C. elegans development in vivo. Moreover, our results suggest that the protein is important for the upregulation of mitochondrial activity during the transition to higher larval stages.
Highlights
Mitochondria are semi-autonomous organelles in eukaryotic organisms, which have a profound role in cell viability through the control of energy production via oxidative phosphorylation (OXPHOS) [1]
We demonstrate that ATAD-3 is a mitochondrial protein and RNA mediated interference (RNAi) induced depletion leads to severe phenotypes, characterized by early larval arrest, gonadal dysfunction, reduced intestinal fat storage and embryonic lethality
Human ATAD3 is a mitochondrial protein, which is thought to be involved in mitochondrial nucleoid organization [10,13]
Summary
Mitochondria are semi-autonomous organelles in eukaryotic organisms, which have a profound role in cell viability through the control of energy production via oxidative phosphorylation (OXPHOS) [1]. The mitochondrial DNA (mtDNA) typically forms a circular, double-stranded molecule that spans about 16,569 base pairs. It encodes 37 genes, all of which are essential for normal mitochondrial function (13 genes encode OXPHOS proteins, 22 encode transfer RNAs, and two encode subunits of ribosomal RNA) [3]. There are much higher copy numbers (,175,000 copies) in mature oocytes [4], which may reflect that a sufficient mtDNA reservoir is required to ensure distribution of mitochondria to the cells of the early embryo.
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