Spatial relationship between mitochondria and the protein quality control system

Identification: Turek, Michal


Description

Spatial relationship between mitochondria and the protein quality control system
 
Michał Turek and Agnieszka Chacińska
University of Warsaw, Warsaw, Poland
 
Mitochondria play several important roles in the cell. Apart from being cell power plants that produce ATP and key depositories for calcium ions, they also take part in various cellular metabolism pathways, for instances heme or steroid synthesis. Malfunctions in any of these processes lead to defects in cell performance which in turns cause pathological states on the organismal level, such as muscular or neurological diseases. However, despite the importance of mitochondria, we still do not fully understand the processes responsible for keeping mitochondria in shape.
The aim of our study is to fully understand the link between healthy mitochondria and the proteasome. In particular, we investigate the spatial relationship between the mitochondria and a very recently discovered protein quality control mechanism, called the Unfolded Protein Response activated by mistargeted proteins (UPRam). We hypothesize that the part of the quality control for mitochondrial proteins exerted by the proteasome is accomplished on the surface of the mitochondria. We address this hypothesis by testing whether the defects in protein import into the mitochondria or in proteins homeostasis influence the abundance of the proteasome complex on the surface of that organelle. Our preliminary results showed increased proteasome activity in a mitochondria-enriched cellular fraction after depletion of DNJ-21 motor protein as well as changes in a proteasome intracellular localization.  We further investigate this phenomenon by using both biochemical and microscopic methods.
Results of this project will expand our knowledge on the process of mitochondrial health regulation. They will especially contribute to the understanding of the quality control of mitochondrial proteins exerted by the proteasome.
 

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