Gerhard Rödel - Mitochondrial biogenesis

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Previous and current research

Mitochondria are essential organelles of eukaryotic cells. They are involved in a number of anabolic and catabolic pathways and play a key role in cellular energy metabolism by oxidative generation of ATP. Biogenesis of mitochondria involves a complex interplay between the genetic systems of the organelle and the nucleus. The few, mostly hydrophobic proteins that are encoded by mitochondrial DNA and translated on mitochondrial ribosomes, constitute subunits of the oxidative phosphorylation system (OXPHOS). The proteins encoded in the nuclear DNA are translated on cytosolic ribosomes and imported into mitochondria. These proteins include structural proteins, enzymes or enzyme subunits, components of the import-, replication-, transcription- and translation-machinery and chaperones. Many basic studies on mitochondrial biogenesis employ yeast cells, because mutants with affected OXPHOS biogenesis can easily be isolated due to their inability to grow on non-fermentable carbon sources like glycerol.

Assembly of OXPHOS enzyme complexes requires a number of specific chaperones. Mutations interfering with the assembly often result in rapid degradation of unassembled subunits. Our group addresses the function of specific proteins in the process of the assembly of OXPHOS complexes. Complex IV (cytochrome c oxidase or COX) assembly depends on the formation of two copper centers (CuA and CuB). Some of the genes which are involved in this process have been identified. Current efforts aim at revealing the exact role of the gene products in this process, and to extend our knowledge to human homologues. To this end we study the effects of RNAi-mediated knockdown of the respective genes in cultured human cells. These findings will help to understand the pathology of human mitochondrial diseases.

Protein phosphorylation in mitochondria is another aspect of our research. Contrary to the situation in mammalian mitochondria, only few data on phosphorylated proteins and the enzymes engaged in the process of phosphorylation and dephosphorylation are available in yeast. We apply a reverse genetic approach by screening the phosphoproteome of mutants lacking candidate kinases and phosphatases with predicted mitochondrial localization. This strategy led to the identification of enzymes that regulate pyruvate dehydrogenase activity via phosphorylation.

A further research topic of our lab is the role of mitochondria in the differentiation of human stem cells (SC). We are studying various parameters of mitochondrial biogenesis and function in the course of SC differentiation and investigate the effects of mitochondrial dysfunction on the formation of mature cells.

Future prospects and goals

Future prospects aim at the detailed characterization of (i) the mitochondrial phosphoproteome, (ii) the mitochondrial copper metabolism in yeasts (S. cerevisiae and S. pombe) and human cell lines, and (iii) the impact of mitochondrial dysfunction on SC differentiation.

Selected publications

Oswald C, Krause-Buchholz U, Rödel G. (2009): Knockdown of human COX17 affects assembly and supramolecular organization of cytochrome c oxidase. J Mol Biology 389:470-479.

Mkandawire M, Pohl A, Gubarevich T, Lapina V, Appelhans D, Rödel G, Pompe W, Schreiber J, Opitz J (2009): Selective targeting of green fluorescent nanodiamond conjugates to mitochondria in HeLa cells. J Biophotonics 2(10):596-606.

Tauche A, Krause-Buchholz U, Rödel G. (2008) : Ubiquinone biosynthesis in Saccharomyces cerevisiae: Molecular organization of O-methylase Coq3p depends on Abc1p/Coq8p. FEMS Yeast Res. 8(8):1263-1275.

Gey U, Czupalla C, Hoflack B, Rödel G, Krause-Buchholz U (2008) : Yeast pyruvate dehydrogenase complex is regulated by a concerted activity of two kinases and two phosphatases. J Biol Chem. 283(15):9759-9767.

Khalimonchuk O, Rödel G (2005 ): Biogenesis of cytochrome c oxidase (Review). Mitochondrion 5:363-388.
Gerhard Rödel
Gerhard Rödel

1981: Dr. rer. nat. University of Munich

1981-1987: Group leader at the University of Munich

1987: Professor for Molecular Biology and Pathology, University of Ulm

1987-1994: Head of the Laboratory of Molecular Biology and Pathology, University of Ulm

1994: Professor for Genetics and Director of the Institute of Genetics, Dresden, University of Technology

2006: Speaker, Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB)