Published 13 February 2006. doi:10.1083/jcb.200505060
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 4, 553-564
Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery
Ann E. Frazier1,2,
Rebecca D. Taylor1,
David U. Mick1,
Bettina Warscheid3,
Nadine Stoepel3,
Helmut E. Meyer3,
Michael T. Ryan2,
Bernard Guiard4, and
Peter Rehling1
1 Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany
2 Department of Biochemistry, La Trobe University, Victoria 3086, Melbourne, Australia
3 Medizinisches Proteom-Center, Ruhr-Universität Bochum, D-44780 Bochum, Germany
4 Laboratoire propre du Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, F-91190 Gif-sur-Yvette, France
Correspondence to Peter Rehling: peter.rehling{at}biochemie.uni-freiburg.de
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 mdm38
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.
Abbreviations used in this paper: BN, blue native; 
, membrane potential; LETM1, Leucine zipperEF-handcontaining transmembrane 1; TIM, translocase of inner mitochondrial membrane; WHS, Wolf-Hirschhorn syndrome.

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