Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery.
Saccharomyces cerevisiae Mdm38 and Ylh47 are homologues of human Letm1, a protein implicated in Wolf-Hirschhorn syndrome. We analyzed the function of Mdm38 and Ylh47 in yeast mitochondria to gain insight into the role of Letm1. We find that mdm38Delta mitochondria have reduced amounts of certain mitochondrially encoded proteins and low levels of complex III and IV and accumulate unassembled Atp6 of complex V of the respiratory chain. Mdm38 is especially required for efficient transport of Atp6 and cytochrome b across the inner membrane, whereas Ylh47 plays a minor role in this process. Both Mdm38 and Ylh47 form stable complexes with mitochondrial ribosomes, similar to what has been reported for Oxa1, a central component of the mitochondrial export machinery. Our results indicate that Mdm38 functions as a component of an Oxa1-independent insertion machinery in the inner membrane and that Mdm38 plays a critical role in the biogenesis of the respiratory chain by coupling ribosome function to protein transport across the inner membrane.
Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany.
Ann E
AE
Frazier
Rebecca D
RD
Taylor
David U
DU
Mick
Bettina
B
Warscheid
Nadine
N
Stoepel
Helmut E
HE
Meyer
Michael T
MT
Ryan
Bernard
B
Guiard
Peter
P
Rehling
D002135:Calcium-Binding Proteins / Q000378:metabolism; D045303:Cytochromes b / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C501004:ATP6 protein, S cerevisiae; D002135:Calcium-Binding Proteins; C488528:LETM1 protein, human; C488529:MDM38 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D029701:Saccharomyces cerevisiae Proteins; C509424:YLH47 protein, S cerevisiae; D045303:Cytochromes b; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases