Protein quality control at the main entry gate for precursor proteins into mitochondria

Identification: MÃ¥rtensson, Christoph


Description

Protein quality control at the main entry gate for precursor proteins into mitochondria
 
Christoph U. Mårtensson1,2, Lars Ellenrieder1,2, Alessia Flörchinger1, Nicole Zufall1, Nikolaus Pfanner1,3, and Thomas Becker1,3
1Institute for Biochemistry and Molecular Biology, University of Freiburg, Germany;
2Faculty of Biology, University of Freiburg, Germany;
3BIOSS Centre for Biological Signalling Studies
      
Mitochondrial functions depend on the uptake of about 1000 different proteins that are synthesized as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the central entry gate for the majority of precursor proteins. After passage through the TOM complex several different protein machineries sort the client proteins into the different mitochondrial subcompartments: the outer and inner membrane, the intermembrane space and the mitochondrial matrix. Defects of protein import have been linked to severe diseases of the nervous system and cardiac and skeletal muscles. Disturbance of the sophisticated protein import system or of the membrane potential as driving force for protein translocation can lead accumulation of precursor proteins at the mitochondrial import machineries. How arrested precursor proteins are retrieved from the protein translocases is not known. Such regeneration of clogged protein translocases, like the TOM complex, is crucial to maintain protein transport into mitochondria.
Using baker´s yeast Saccharomyces cerevisiae as model organism, we report novel insights into the removal of stalled precursor proteins from the TOM complex. We identified an unexpected role of the ubiquitin proteasome system for the degradation of non-imported precursor proteins. Excitingly, we found a key player of the ubiquitin proteasome system as a novel interaction partner of the TOM complex in pull down studies. This interaction is critical for the recruitment of further factors of the ubiquitin proteasome system leading to the extraction of the precursor from the TOM complex for proteasomal degradation.
In conclusion, we discovered a novel mechanism how the cell copes with clogged TOM complex of mitochondria. Our findings shed light into the fundamental question about quality control of mitochondrial protein import.

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