Anton, Vincent ORCID: 0000-0003-3008-6346, Buntenbroich, Ira, Schuster, Ramona ORCID: 0000-0002-2227-3718, Babatz, Felix, Simoes, Tania, Altin, Selver, Calabrese, Gaetano ORCID: 0000-0002-2212-5280, Riemer, Jan, Schauss, Astrid and Escobar-Henriques, Mafalda ORCID: 0000-0002-0879-3119 (2019). Plasticity in salt bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition. Life Sci. Alliance, 2 (6). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

Full text not available from this repository.

Abstract

Mitofusins are dynamin-related GTPases that drive mitochondrial fusion by sequential events of oligomerization and GTP hydrolysis, followed by their ubiquitylation. Here, we show that fusion requires a trilateral salt bridge at a hinge point of the yeast mitofusin Fzo1, alternatingly forming before and after GTP hydrolysis. Mutations causative of Charcot-Marie-Tooth disease massively map to this hinge point site, underlining the disease relevance of the trilateral salt bridge. A triple charge swap rescues the activity of Fzo1, emphasizing the close coordination of the hinge residues with GTP hydrolysis. Subsequently, ubiquitylation of Fzo1 allows the AAA-ATPase ubiquitin-chaperone Cdc48 to resolve Fzo1 clusters, releasing the dynamin for the next fusion round. Furthermore, cross-complementation within the oligomer unexpectedly revealed ubiquitylated but fusion-incompetent Fzo1 intermediates. However, Cdc48 did not affect the ubiquitylated but fusion-incompetent variants, indicating that Fzo1 ubiquitylation is only controlled after membrane merging. Together, we present an integrated model on how mitochondrial outer membranes fuse, a critical process for their respiratory function but also putatively relevant for therapeutic interventions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Anton, VincentUNSPECIFIEDorcid.org/0000-0003-3008-6346UNSPECIFIED
Buntenbroich, IraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuster, RamonaUNSPECIFIEDorcid.org/0000-0002-2227-3718UNSPECIFIED
Babatz, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simoes, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altin, SelverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calabrese, GaetanoUNSPECIFIEDorcid.org/0000-0002-2212-5280UNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schauss, AstridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Escobar-Henriques, MafaldaUNSPECIFIEDorcid.org/0000-0002-0879-3119UNSPECIFIED
URN: urn:nbn:de:hbz:38-125737
DOI: 10.26508/lsa.201900491
Journal or Publication Title: Life Sci. Alliance
Volume: 2
Number: 6
Date: 2019
Publisher: LIFE SCIENCE ALLIANCE LLC
Place of Publication: COLD SPRING HARBOR
ISSN: 2575-1077
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REGULATE MITOCHONDRIAL FUSION; STRUCTURAL BASIS; PROTEIN; REQUIRES; OUTER; MFN1; BIOGENESIS; DYNAMICS; VECTORS; FISSIONMultiple languages
BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12573

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item