C. elegans ATAD-3 is essential for mitochondrial activity and development.
BACKGROUND
Mammalian ATAD3 is a mitochondrial protein, which is thought to play an important role in nucleoid organization. However, its exact function is still unresolved.


RESULTS
Here, 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.


CONCLUSIONS
In 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.
Hoffmann
Michael
M
Department of General Pediatrics, University Children's Hospital, Heinrich-Heine-University, Düsseldorf, Germany.
Bellance
Nadège
N
Rossignol
Rodrigue
R
Koopman
Werner J H
WJ
Willems
Peter H G M
PH
Mayatepek
Ertan
E
Bossinger
Olaf
O
Distelmaier
Felix
F
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D006801:Humans; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
C549686:ATAD3A protein, human; C519737:ATAD3B protein, human; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C546126:atad-3 protein, C elegans; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities