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Biogenesis and Architecture of Mitochondria

 
Mitochondria are essential for the viability of eukaryotic cells. They play central functions in cellular ATP synthesis, the metabolism of amino acids and lipids, the biosynthesis of heme and Fe/S clusters, as well as in programmed cell death (apoptosis). Mitochondria consist of four subcompartments: outer membrane, intermembrane space, inner membrane and matrix. The inner membrane possesses a characteristic architecture with tubular invaginations (cristae) that increase the membrane surface several-fold. Defects of mitochondrial function and homeostasis lead to severe human diseases, in particular of the nervous system, heart and muscles.
 
Mitochondria contain more than 1,000 different proteins. A small number of proteins are synthesized inside mitochondria. 99% of mitochondrial proteins, however, are encoded by nuclear genes and are synthesized as precursor proteins on cytosolic ribosomes. The precursor proteins contain targeting signals that direct them to mitochondria and to their functional destination in the mitochondrial subcompartments. Most precursor proteins are translocated into mitochondria by the main protein entry gate, the translocase of the outer mitochondrial membrane (TOM). Subsequently, the precursor proteins are transferred to distinct machineries that promote their intramitochondrial sorting and assembly.
 
Figure-Pfanner
 
Our studies focus on the following topics:
 
  • Targeting of precursor proteins from the cytosol into mitochondria: molecular mechanisms and regulation of mitochondrial preprotein translocases
  • Cooperation of translocases during transport and assembly of mitochondrial proteins: dynamic supercomplexes and protein networks
  • Molecular architecture of the mitochondrial membranes: machineries forming membrane contact sites and maintaining the characteristic shape of mitochondria
 
 

molekulare Fässer

Protein Team Produces Molecular Barrels
 
Funding
German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)
Collaborative Research Center 746 (SFB 746)
Cluster of Excellence – BIOSS Centre of Biological Signalling Studies
Spemann Graduate School of Biology and Medicine (SGBM)
Hector Fellow Academy

 

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