Schuster, Ramona ORCID: 0000-0002-2227-3718, Anton, Vincent ORCID: 0000-0003-3008-6346, Simoes, Tania, Altin, Selver, den Brave, Fabian ORCID: 0000-0001-6955-4616, Hermanns, Thomas ORCID: 0000-0001-5350-7479, Hospenthal, Manuela ORCID: 0000-0003-1175-6826, Komander, David, Dittmar, Gunnar ORCID: 0000-0003-3647-8623, Dohmen, R. Juergen ORCID: 0000-0002-5756-6780 and Escobar-Henriques, Mafalda (2020). Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation. Life Sci. Alliance, 3 (1). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

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Abstract

Mitochondria are essential organelles whose function is upheld by their dynamic nature. This plasticity is mediated by large dynamin-related GTPases, called mitofusins in the case of fusion between two mitochondrial outer membranes. Fusion requires ubiquitylation, attached to K398 in the yeast mitofusin Fzo1, occurring in atypical and conserved forms. Here, modelling located ubiquitylation to alpha 4 of the GTPase domain, a critical helix in Ras-mediated events. Structure-driven analysis revealed a dual role of K398. First, it is required for GTP-dependent dynamic changes of alpha 4. Indeed, mutations designed to restore the conformational switch, in the absence of K398, rescued wild-type-like ubiquitylation on Fzo1 and allowed fusion. Second, K398 is needed for Fzo1 recognition by the pro-fusion factors Cdc48 and Ubp2. Finally, the atypical ubiquitylation pattern is stringently required bilaterally on both involved mitochondria. In contrast, exchange of the conserved pattern with conventional ubiquitin chains was not sufficient for fusion. In sum, alpha 4 lysines from both small and large GTPases could generally have an electrostatic function for membrane interaction, followed by posttranslational modifications, thus driving membrane fusion events.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schuster, RamonaUNSPECIFIEDorcid.org/0000-0002-2227-3718UNSPECIFIED
Anton, VincentUNSPECIFIEDorcid.org/0000-0003-3008-6346UNSPECIFIED
Simoes, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altin, SelverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
den Brave, FabianUNSPECIFIEDorcid.org/0000-0001-6955-4616UNSPECIFIED
Hermanns, ThomasUNSPECIFIEDorcid.org/0000-0001-5350-7479UNSPECIFIED
Hospenthal, ManuelaUNSPECIFIEDorcid.org/0000-0003-1175-6826UNSPECIFIED
Komander, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dittmar, GunnarUNSPECIFIEDorcid.org/0000-0003-3647-8623UNSPECIFIED
Dohmen, R. JuergenUNSPECIFIEDorcid.org/0000-0002-5756-6780UNSPECIFIED
Escobar-Henriques, MafaldaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-351752
DOI: 10.26508/lsa.201900476
Journal or Publication Title: Life Sci. Alliance
Volume: 3
Number: 1
Date: 2020
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 Biology > Botanical Institute
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MITOCHONDRIAL FUSION; SACCHAROMYCES-CEREVISIAE; FLUORESCENT PROTEINS; RAS PROTEIN; UBIQUITIN; DOMAIN; PROTEASOME; DYNAMICS; ORIENTATION; REQUIRESMultiple languages
BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/35175

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