Proteins can perform their biological functions only if they fold into the correct three-dimensional form. As a rule, this conformation is largely determined by the amino-acid sequence of a protein, but many proteins require accessory factors to fold properly. If protein folding is perturbed (as in the presence of oxidative stress, for instance), not only do inactive proteins accumulate, they can also give rise to highly toxic aggregates. However, cells have evolved a quality-control mechanism that monitors protein folding. If a misfolded protein is detected, a process known as the Unfolded Protein Response (UPR) is activated, which ensures that the protein is degraded and normal cell function is restored. Using the nematode Caenorhabditis elegans as their experimental model, LMU biologists led by Stéphane Rolland have asked how this stress response is triggered in mitochondria, and identified a fundamental mechanism that regulates the UPR in these organelles. Their findings appear in the leading journal Cell Reports.
The UPR machinery is found in several of the diverse membrane-bounded intracellular compartments found in eukaryotic cells, so that errors in protein folding anywhere in the cell can be swiftly dealt with. The mitochondria, which provide the cell with chemical energy, represent one such compartment. Earlier studies on C. elegans had indicated that the transcription factor ATFS-1 plays an important role in initiating the UPR in these organelles. Normally, ATFS-1 is imported into the mitochondria and rapidly degraded. However, when mitochondria are under stress, the protein is re-routed to the cell nucleus. There it activates the transcription of genes which code for proteins that implement the UPR in mitochondria. Moreover, this signaling pathway has been evolutionarily conserved, at least in part, from nematodes to mammals.
Nature - Signal - Stress
"Up to now, the precise nature of the signal that triggers this cellular stress...
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