Dissolving the traffic jam – how cells counteract the blockage of mitochondrial protein entry gates

Identification: Boos, Felix



Dissolving the traffic jam how cells counteract the blockage of mitochondrial protein entry gates
Felix Boos1, Carina Groh1, Adrian Gackstatter1, Eva Zöller1, Ferris Jung2, Vladimir Benes2, Johannes Herrmann1
1University of Kaiserslautern, Cell Biology; 2European Molecular Biology Laboratory Heidelberg, Genomics Core Facility
The processes by which mitochondrial precursor proteins are imported are well studied. However, little is known about how cells regulate this process, adapt their targeting system to changing intracellular conditions and possibly deal with situations in which the capacity of the import system is overloaded.
To understand how cells react to systemic mitochondrial import stress, we developed a yeast strain in which we can induce blockage of the import complexes. The strain expresses a “clogger” protein that is targeted to mitochondria and forms a tightly folded domain that cannot efficiently pass the translocation pore, thereby transiently and competitively blocking it.
Using this strain as a model, we employed next generation sequencing (RNAseq) to monitor the transcriptomic changes upon induction of the clogger. We acquired time-resolved expression data on complete genome level with more than 1.6 billion sequenced reads in total.
We were thus able to identify a hitherto undescribed cellular stress response: Chaperones of the Hsp70 and Hsp90 family are upregulated very early in the response, followed by the proteasome. This might help to cope with accumulating precursor proteins in the cytosol by keeping them soluble or eventually degrade them. On the other hand, genes associated with oxidative phosphorylation are quickly downregulated, possibly to reduce the workload of the overstrained translocation machinery and to prevent further accumulation of non-imported proteins. In line with this, we observed decreased transcript levels of protein subunits of the cytosolic ribosome.
Furthermore, based on the high-resolution expression profiles, we can make predictions about the transcription factors involved in the underlying signaling cascade which we aim to verify in the future.
In summary, we describe a novel response mechanism which most likely integrates both organelle-specific stress reactions and general cellular stress response pathways.
We are grateful to the Joachim Herz Stiftung and the Deutsche Forschungsgemeinschaft for funding.



Credits: None available.

You must be logged in and own this product in order to post comments.