Abstract
The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR.
Highlights
In a single cell organism like the yeast Saccharomyces cerevisiae, metabolism and stress response are tightly intertwined[1]
We found a sensitivity of the TRR1 deletion mutant to rapamycin that leads to the discovery of a new function of Trr1p in the regulation of the TORC1 activity and in the activation of autophagy
In order to study the impact of cytosolic thioredoxin reductase on chronological life span in a variety of environmental growth conditions, the TRR1 gene was deleted in haploid wine yeast C921 to allow us to test the relevance of this gene on different growth conditions as laboratory S. cerevisiae strains do not perform well under grape juice fermentation[22]
Summary
In a single cell organism like the yeast Saccharomyces cerevisiae, metabolism and stress response are tightly intertwined[1]. The active complex regulates many processes, promotes ribosome biosynthesis and translation through AGC kinase Sch[9] activity, but prevents a general stress response (as explained below), and the use of non preferred nitrogen sources and autophagy. All these mechanisms are required to achieve full viability when nutrients are scarce and growth has ceased, a situation that cells face during chronological aging. Oxidative stress is relevant for chronological aging during grape juice fermentation[15], in combination with nutrient-sensing pathways, because the chemical inhibition of TORC1 extends longevity under these conditions[16]. Trr1p controls the protein levels of TOR kinase Tor2p, which suggests a direct role in the amount or activity of the TORC1 complex
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