Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schuster, Ramona UNSPECIFIED orcid.org/0000-0002-2227-3718 UNSPECIFIED Anton, Vincent UNSPECIFIED orcid.org/0000-0003-3008-6346 UNSPECIFIED Simoes, Tania UNSPECIFIED UNSPECIFIED UNSPECIFIED Altin, Selver UNSPECIFIED UNSPECIFIED UNSPECIFIED den Brave, Fabian UNSPECIFIED orcid.org/0000-0001-6955-4616 UNSPECIFIED Hermanns, Thomas UNSPECIFIED orcid.org/0000-0001-5350-7479 UNSPECIFIED Hospenthal, Manuela UNSPECIFIED orcid.org/0000-0003-1175-6826 UNSPECIFIED Komander, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Dittmar, Gunnar UNSPECIFIED orcid.org/0000-0003-3647-8623 UNSPECIFIED Dohmen, R. Juergen UNSPECIFIED orcid.org/0000-0002-5756-6780 UNSPECIFIED Escobar-Henriques, Mafalda UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MITOCHONDRIAL FUSION; SACCHAROMYCES-CEREVISIAE; FLUORESCENT PROTEINS; RAS PROTEIN; UBIQUITIN; DOMAIN; PROTEASOME; DYNAMICS; ORIENTATION; REQUIRES Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/35175