Molecular function of Mdm38 in protein export and biogenesis of respiratory chain complexes of the inner mitochondrial membrane

• Applicant: Professor Dr. Peter Rehling
• Subject Area: Cell Biology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 37395318

Mdm38 is the S. cerevisiae homolog of the human Letm1, a protein that has been implicated in the pathogenesis of the Wolf-Hirschhorn Syndrome. We have found that Mdm38 is required for the biogenesis of respiratory chain complexes. The inner membrane protein Mdm38 interacts with mitochondrial ribosomes and participates in protein export across the inner mitochondrial membrane. Since the role of Mdm38 in these processes is unknown, we will analyze the molecular function of Mdm38 in protein transport and complex assembly in this project. Therefore, we will address the function of Mdm38 in the process of respiratory chain complex assembly with an in organello approach based on import and export analyses in mutant mitochondria. A central question is the molecular function of the Mdm38-ribosome association. Therefore, we will dissect the molecular interactions of Mdm38 with mitochondrial ribosomes and analyze other Mdm38 interacting proteins, which are part of the Mdm38 complex. It will be of particular interest to determine if Letm1 fulfills similar functions in human cells as Mdm38 in yeast. Therefore we will use an RNAi based approach to reduce levels of Letm1 in human cells and analyze mitochondrial functions such as morphology and respiratory chain complexes in these cells. Our analysis should allow novel insights into the function of Mdm38, the biogenesis of respiratory chain complexes and the molecular basis of a human disease.

• DFG Programme: Research Grants