Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along 
independent pathways

Anton, F.; Dittmar, G.; Langer, T.; Escobar-Henriques, M.

doi:10.1016/j.molcel.2012.12.003

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along independent pathways

MPS-Authors

/persons/resource/persons278030

Langer, T.
Department Langer - Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Max Planck Society;

External Resource

https://www.ncbi.nlm.nih.gov/pubmed/23317502
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Anton, F., Dittmar, G., Langer, T., & Escobar-Henriques, M. (2013). Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along independent pathways. Mol Cell, 49(3), 487-98. doi:10.1016/j.molcel.2012.12.003.

Cite as: https://hdl.handle.net/21.11116/0000-000B-B3F3-8

Abstract

Mitofusins, conserved dynamin-related GTPases in the mitochondrial outer membrane, mediate the fusion of mitochondria. Here, we demonstrate that the activity of the mitofusin Fzo1 is regulated by sequential ubiquitylation at conserved lysine residues and by the deubiquitylases Ubp2 and Ubp12. Ubp2 and Ubp12 recognize distinct ubiquitin chains on Fzo1 that have opposing effects on mitochondrial fusion. Ubp2 removes ubiquitin chains that initiate proteolysis of Fzo1 and inhibit fusion. Ubp12 recognizes ubiquitin chains that stabilize Fzo1 and promote mitochondrial fusion. Self-assembly of dynamin-related GTPases is critical for their function. Ubp12 deubiquitylates Fzo1 only after oligomerization. Moreover, ubiquitylation at one monomer activates ubiquitin chain formation on another monomer. Thus, regulation of mitochondrial fusion involves ubiquitylation of mitofusin at distinct lysine residues, intermolecular crosstalk between mitofusin monomers, and two deubiquitylases that act as regulatory and quality control enzymes.