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http://ipicyt.repositorioinstitucional.mx/jspui/handle/1010/2499| Alanine Represses gamma-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae | |
| DARIEL MARQUEZ GUTIERREZ XIMENA MARTINEZ DE LA ESCALERA FANJUL MOHAMMED EL HAFIDI BENTLAKDER BEATRIZ AGUIRRE LOPEZ Lina Raquel Riego Ruiz MARIA ALICIA GONZALEZ MANJARREZ | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.3389/fmicb.2021.695382 | |
| GABA shunt Stress response Respiratory metabolism Mitochondrial genes Transcriptional coregulators | |
| "The gamma-aminobutyric acid (GABA) shunt constitutes a conserved metabolic route generating nicotinamide adenine dinucleotide phosphate (NADPH) and regulating stress response in most organisms. Here we show that in the presence of GABA, Saccharomyces cerevisiae produces glutamate and alanine through the irreversible action of Uga1 transaminase. Alanine induces expression of alanine transaminase (ALT1) gene. In an alt1 Delta mutant grown on GABA, alanine accumulation leads to repression of the GAD1, UGA1, and UGA2 genes, involved in the GABA shunt, which could result in growth impairment. Induced ALT1 expression and negative modulation of the GABA shunt by alanine constitute a novel regulatory circuit controlling both alanine biosynthesis and catabolism. Consistent with this, the GABA shunt and the production of NADPH are repressed in a wild-type strain grown in alanine, as compared to those detected in the wild-type strain grown on GABA. We also show that heat shock induces alanine biosynthesis and ALT1, UGA1, UGA2, and GAD1 gene expression, whereas an uga1 Delta mutant shows heat sensitivity and reduced NADPH pools, as compared with those observed in the wild-type strain. Additionally, an alt1 Delta mutant shows an unexpected alanine-independent phenotype, displaying null expression of mitochondrial COX2, COX3, and ATP6 genes and a notable decrease in mitochondrial/nuclear DNA ratio, as compared to a wild-type strain, which results in a petite phenotype. Our results uncover a new negative role of alanine in stress defense, repressing the transcription of the GABA shunt genes, and support a novel Alt1 moonlighting function related to the maintenance of mitochondrial DNA integrity and mitochondrial gene expression." | |
| Frontiers Media S.A. | |
| 2021 | |
| Artículo | |
| Márquez D, Escalera-Fanjul X, el Hafidi M, Aguirre-LÓpez B, Riego-Ruiz L and González A (2021) Alanine Represses γ-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae. Front. Microbiol. 12:695382. doi: 10.3389/fmicb.2021.695382 | |
| MICROBIOLOGÍA | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Publicaciones Científicas Biología Molecular |
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