Regulation of mitochondrial fusion by the F-box protein Mdm30 involves proteasome-independent turnover of Fzo1

被引:97
作者
Escobar-Henriques, Mafalda
Westermann, Benedikt
Langer, Thomas [1 ]
机构
[1] Univ Cologne, Inst Genet, D-50923 Cologne, Germany
[2] Univ Cologne, Ctr Mol Med, D-50923 Cologne, Germany
[3] Univ Bayreuth, Inst Cell Biol, D-95447 Bayreuth, Germany
关键词
D O I
10.1083/jcb.200512079
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mitochondrial morphology depends on balanced fusion and fission events. A central component of the mitochondrial fusion apparatus is the conserved GTPase Fzo1 in the outer membrane of mitochondria. Mdm30, an F-box protein required for mitochondrial fusion in vegetatively growing cells, affects the cellular Fzo1 concentration in an unknown manner. We demonstrate that mitochondrial fusion requires a tight control of Fzo1 levels, which is ensured by Fzo1 turnover. Mdm30 binds to Fzo1 and, dependent on its F-box, mediates proteolysis of Fzo1. Unexpectedly, degradation occurs along a novel proteolytic pathway not involving ubiquitylation, Skp1-Cdc53-F-box (SCF) E3 ubiquitin ligase complexes, or 26S proteasomes, indicating a novel function of an F-box protein. This contrasts to the ubiquitin and proteasome-dependent turnover of Fzo1 in alpha-factor arrested yeast cells. Our results therefore reveal not only a critical role of Fzo1 degradation for mitochondrial fusion in vegetatively growing cells but also the existence of two distinct proteolytic pathways for the turnover of mitochondrial outer membrane proteins.
引用
收藏
页码:645 / 650
页数:6
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