The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes

Benoît Gilquin, Emmanuel Taillebourg, Nadia Cherradi, Arnaud Hubstenberger, Olivia Gay, Nicolas Merle, Nicole Assard, Marie Odile Fauvarque, Shiho Tomohiro, Osamu Kuge, Jacques Baudier

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Abstract

Dynamic interactions between components of the outer (OM) and inner (IM) membranes control a number of critical mitochondrial functions such as channeling of metabolites and coordinated fission and fusion. We identify here the mitochondrial AAA+ ATPase protein ATAD3A specific to multicellular eukaryotes as a participant in these interactions. The N-terminal domain interacts with the OM. A central transmembrane segment (TMS) anchors the protein in the IM and positions the C-terminal AAA+ ATPase domain in the matrix. Invalidation studies in Drosophila and in a human steroidogenic cell line showed that ATAD3A is required for normal cell growth and cholesterol channeling at contact sites. Using dominant-negative mutants, including a defective ATP-binding mutant and a truncated 50-amino-acid N-terminus mutant, we showed that ATAD3A regulates dynamic interactions between the mitochondrial OM and IM sensed by the cell fission machinery. The capacity of ATAD3A to impact essential mitochondrial functions and organization suggests that it possesses unique properties in regulating mitochondrial dynamics and cellular functions in multicellular organisms.

Original languageEnglish
Pages (from-to)1984-1996
Number of pages13
JournalMolecular and cellular biology
Volume30
Issue number8
DOIs
Publication statusPublished - Apr 2010

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Gilquin, B., Taillebourg, E., Cherradi, N., Hubstenberger, A., Gay, O., Merle, N., ... Baudier, J. (2010). The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes. Molecular and cellular biology, 30(8), 1984-1996. https://doi.org/10.1128/MCB.00007-10