Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

Official URL:https://doi.org/10.1016/j.molcel.2012.12.003
PubMed:View item in PubMed
Creators Name:Anton, F. and Dittmar, G. and Langer, T. and Escobar-Henriques, M.
Journal Title:Molecular Cell
Journal Abbreviation:Mol Cell
Volume:49
Number:3
Page Range:487-498
Date:7 February 2013
Keywords:Amino Acid Sequence, Biological Models, Conserved Sequence, Endopeptidases, GTP Phosphohydrolases, Lysine, Membrane Proteins, Mitochondria, Mitochondrial Dynamics, Molecular Sequence Data, Proteasome Endopeptidase Complex, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitination
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.
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Item Type:Article

Repository Staff Only: item control page

Open Access
MDC Library