Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation.
Ups1p, Ups2p, and Ups3p are three homologous proteins that control phospholipid metabolism in the mitochondrial intermembrane space (IMS). The Ups proteins are atypical IMS proteins in that they lack the two major IMS-targeting signals, bipartite presequences and cysteine motifs. Here, we show that Ups protein import is mediated by another IMS protein, Mdm35p. In vitro import assays show that import of Ups proteins requires Mdm35p. Loss of Mdm35p led to a decrease in steady state levels of Ups proteins in mitochondria. In addition, mdm35Delta cells displayed a similar phenotype to ups1Deltaups2Deltaups3Delta cells. Interestingly, unlike typical import machineries, Mdm35p associated stably with Ups proteins at a steady state after import. Demonstrating that Mdm35p is a functional component of Ups-Mdm35p complexes, restoration of Ups protein levels in mdm35Delta mitochondria failed to restore phospholipid metabolism. These findings provide a novel mechanism in which the formation of functional protein complexes drives mitochondrial protein import.
Tamura
Yasushi
Y
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Iijima
Miho
M
Sesaki
Hiromi
H
D017353:Gene Deletion; D050296:Microbial Viability; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
C552370:Mdm35 protein, S cerevisiae; D024101:Mitochondrial Proteins; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C512497:Ups1 protein, S cerevisiae; C542159:Ups2 protein, S cerevisiae; C552369:Ups3 protein, S cerevisiae