An Investigation of TDA1 Deficiency in Saccharomyces cerevisiae During Diauxic Growth

TL;DR

This study shows that the TDA1 gene in yeast regulates mitochondrial translation during the diauxic shift by controlling the HAP-complex, not by interacting with Mig1p.

Contribution

The study clarifies TDA1's role in mitochondrial translation regulation during the diauxic shift, challenging previous assumptions about its interaction with Mig1p.

Findings

TDA1 deletion leads to upregulation of mitochondrial translation genes during the post-diauxic shift phase.

TDA1 does not appear to interact with Mig1p in glucose repression, contrary to prior models.

TDA1 likely represses HAP-complex subunits to regulate mitochondrial translation.

Abstract

Tda1p is a protein kinase in Saccharomyces cerevisiae. Here we investigate the function of TDA1 during the diauxic shift using transcriptomics. We compared the gene expression in the deletion mutant tda1∆ and the reference strain (BY4741) during both the aerobic fermentation phase (log phase), and the respiratory phase (post‐diauxic shift phase, PDS) in three separate independent experiments. We found: Differential gene expression analysis showed that compared to the reference strain, the tda1∆ mutant exhibited an upregulation of the glucose repressed hexose transporter HXT6 during the log phase, and upregulation of mitochondrial proteins and genes related to mitochondrial translation during the PDS phase. Gene set enrichment analysis showed an enrichment in mitochondrial translation in the PDS phase for the deletion mutant tda1∆, but not for the reference strain. Transcription factor analysis showed that the enrichment of Mig1p repressed genes was not statistically significant in TDA1 deletion mutants for neither log‐phase nor PDS‐phase. This conflicted with the previously suggested model that argued for an interaction between Tda1p and Mig1p. Instead, transcription factor analysis showed an enrichment of genes regulated by the HAP‐complex, which regulates mitochondrial translation, during the PDS‐phase in the tda1∆ mutant. The combined evidence from this study indicates that Tda1p does not participate in Mig1p‐mediated glucose repression. Instead, we propose that it is involved in the regulation of mitochondrial translation by repressing the expression of HAP complex subunits.

Tda1p is a protein kinase in Saccharomyces cerevisiae with unknown/disputed function. Its role during the diauxic shift was investigated in three independent transcriptomics experiment. From the evidence that was consistent across the experiments, we propose that TDA1 is involved in regulation of mitochondrial translation by repressing the expression of HAP‐complex subunits.

This study investigated TDA1, a kinase with disputed biological function, using transcriptomics data.Genes related to “Mitochondrial translation” were enriched in tda1∆ post‐diauxic shift.A subunit of the HAP‐complex, which induces mitochondrial translation, was upregulated in tda1∆.Genes targeted by the HAP‐complex were enriched in tda1∆.The combined evidence suggests that TDA1 regulates mitochondrial translation during the diauxic shift by repressing the HAP‐complex.

This study investigated TDA1, a kinase with disputed biological function, using transcriptomics data.

Genes related to “Mitochondrial translation” were enriched in tda1∆ post‐diauxic shift.

A subunit of the HAP‐complex, which induces mitochondrial translation, was upregulated in tda1∆.

Genes targeted by the HAP‐complex were enriched in tda1∆.

The combined evidence suggests that TDA1 regulates mitochondrial translation during the diauxic shift by repressing the HAP‐complex.

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