The AAA+ ATPase ATAD3A Controls Mitochondrial Dynamics at the Interface of the Inner and Outer Membranes
Benoit Gilquin
(1)
,
Emmanuel Taillebourg
(2)
,
Nadia Cherradi
(3)
,
Arnaud Hubstenberger
(4)
,
Olivia Gay
(1)
,
Nicolas Merle
(5)
,
Nicole Assard
(1)
,
Marie-Odile Fauvarque
(2)
,
Shiho Tomohiro
,
Osamu Kuge
,
Jacques Baudier
(1)
Nadia Cherradi
- Fonction : Auteur
- PersonId : 180012
- IdHAL : nadia-cherradi
- ORCID : 0000-0002-4292-774X
- IdRef : 185869831
Marie-Odile Fauvarque
- Fonction : Auteur
- PersonId : 176127
- IdHAL : marie-odile-fauvarque
- ORCID : 0000-0001-5020-3701
- IdRef : 097704229
Shiho Tomohiro
- Fonction : Auteur
Osamu Kuge
- Fonction : Auteur
Résumé
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.
Domaines
Sciences de l'Homme et SociétéFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
The AAA+ ATPase ATAD3A Controls Mitochondrial Dynamics at the Interface of the Inner and Outer Membranes
|
Résumé |
en
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.
|
Auteur(s) |
Benoit Gilquin
1
, Emmanuel Taillebourg
2
, Nadia Cherradi
3
, Arnaud Hubstenberger
4
, Olivia Gay
1
, Nicolas Merle
5
, Nicole Assard
1
, Marie-Odile Fauvarque
2
, Shiho Tomohiro
, Osamu Kuge
, Jacques Baudier
1
1
BGE - UMR S1038 -
Laboratoire de Biologie à Grande Échelle
( 226010 )
- 17, Rue des Martyrs 38054 Grenoble cedex 09
- France
2
GenChem -
Genetics and Chemogenomics
( 553452 )
- 17, avenue des Martyrs 38 054 Grenoble cedex 09
- France
3
LAPV -
Angiogenèse hormono-regulée et angiogenèse tumorale
( 40553 )
- France
4
LBD -
Laboratoire de Biologie du Développement
( 1151 )
- bat. C-30, 7° Etage, bte.24 9 Quai Saint-Bernard 75252 PARIS CEDEX 05
- France
5
C2P2 -
Laboratoire de Chimie, Catalyse, Polymères et Procédés, R 5265
( 191041 )
- 43, Bd. du 11 Novembre 1918, Villeurbanne F-69616,
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2010-03-25
|
Volume |
30
|
Numéro |
8
|
Page/Identifiant |
1984-1996
|
Domaine(s) |
|
DOI | 10.1128/MCB.00007-10 |
Pubmed Id | 20154147 |
PubMed Central | PMC2849464 |
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