Universität zu Köln

Mottie, Sevan, Riemer, Jan, Wideman, Jeremy G. and McBride, Heidi M. (2018). A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space. J. Cell Biol., 217 (2). S. 507 - 516. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Bioinformatic analysis showed that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain. This prediction contradicts the current models, suggesting that both animal and fungal proteins share one topology. This newly predicted topology of Mfn1 and Mfn2 was demonstrated biochemically, confirming that the C-terminal, redox-sensitive cysteine residues reside within the intermembrane space (IMS). Functional experiments established that redox-mediated disulfide modifications within the IMS domain are key modulators of reversible Mfn oligomerization that drives fusion. Together, these results lead to a revised understanding of Mfns as single-spanning outer membrane proteins with an N-out-C-in orientation, providing functional insight into the IMS contribution to redox-regulated fusion events.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mottie, Sevan UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wideman, Jeremy G. UNSPECIFIED UNSPECIFIED UNSPECIFIED McBride, Heidi M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-196523
DOI:	10.1083/jcb.201611194
Journal or Publication Title:	J. Cell Biol.
Volume:	217
Number:	2
Page Range:	S. 507 - 516
Date:	2018
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
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:	Keywords Language INNER-MEMBRANE-FUSION; MAMMALIAN-CELLS; PROTEIN IMPORT; MIXED MODELS; TOM COMPLEX; DYNAMICS; STRESS; HYPERFUSION; TRANSLOCASE; GENERATION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19652