Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation.
Biogenesis of respiratory chain complexes depends on the expression of mitochondrial-encoded subunits. Their synthesis occurs on membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in expression of mitochondrial translation products are among the major causes of mitochondrial disorders. Mdm38 is related to Letm1, a protein affected in Wolf-Hirschhorn syndrome patients. Like Mba1 and Oxa1, Mdm38 is an inner membrane protein that interacts with ribosomes and is involved in respiratory chain biogenesis. We find that simultaneous loss of Mba1 and Mdm38 causes severe synthetic defects in the biogenesis of cytochrome reductase and cytochrome oxidase. These defects are not due to a compromised membrane binding of ribosomes but the consequence of a mis-regulation in the synthesis of Cox1 and cytochrome b. Cox1 expression is restored by replacing Cox1-specific regulatory regions in the mRNA. We conclude, that Mdm38 and Mba1 exhibit overlapping regulatory functions in translation of selected mitochondrial mRNAs.
Bauerschmitt
Heike
H
Zellbiologie, Universität Kaiserslautern, 67663 Kaiserslautern, Germany.
Mick
David U
DU
Deckers
Markus
M
Vollmer
Christine
C
Funes
Soledad
S
Kehrein
Kirsten
K
Ott
Martin
M
Rehling
Peter
P
Herrmann
Johannes M
JM
D000332:Aerobiosis / Q000187:drug effects; D045303:Cytochromes b / Q000096:biosynthesis; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009550:Nigericin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
C100490:MBA1 protein, S cerevisiae; C488529:MDM38 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D045303:Cytochromes b; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D009550:Nigericin