title: MICS-1 interacts with mitochondrial ATAD-3 and modulates lifespan in C. elegans.
abstract: Caenorhabditis elegans open reading frame T21C9.1 encodes an uncharacterized protein, which is here named MICS-1 (mitochondrial scaffolding protein-1). It is predicted to be the homolog of human outer mitochondrial membrane protein 25 (OMP25 or synaptojanin-2-binding protein), which is a PDZ domain containing protein with a putative role in cellular stress response pathways. Here, we provide evidence that MICS-1 is an interacting partner of mitochondrial protein ATAD-3 (homologue of human ATAD3), which is essential for C. elegans development. We demonstrate that mics-1(RNAi) animals or mics-1 mutants display enhanced longevity with an increased mean lifespan of up to 54% compared to control animals. Of note, also atad-3(RNAi) promoted longevity, although to a lesser extend (29% compared to controls). In addition, thermal stress of mics-1 mutants induced low reactive oxygen species (ROS) production, whereas atad-3(RNAi) animals were highly sensitive to this assay, displaying drastically increased ROS levels. Further studies revealed that MICS-1 and ATAD-3 associated longevity was partially dependent on the presence of DAF-16. However, for both conditions, we also found a DAF-16 independent extension of lifespan. Finally, we observed an additional lifespan extension in mics-1 mutants when subjected to atad-3(RNAi) whereas heat induced ROS production was even aggravated under this condition. This suggests (partially) independent effects of MICS-1 and ATAD-3 on lifespan and ROS production in vivo.
authors.affiliation: Department of General Pediatrics and Neonatology, University Children's Hospital, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Honnen
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.forename: Wim
authors.initials: W
authors.lastname: Wätjen
authors.forename: Werner J H
authors.initials: WJ
authors.lastname: Koopman
authors.forename: Olaf
authors.initials: O
authors.lastname: Bossinger
authors.forename: Felix
authors.initials: F
authors.lastname: Distelmaier
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006358:Hot Temperature; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C546126:atad-3 protein, C elegans