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Mmi1, the Yeast Ortholog of Mammalian Translationally Controlled Tumor Protein (TCTP), Negatively Affects Rapamycin-Induced Autophagy in Post-Diauxic Growth Phase.

ABSTRACT: Translationally controlled tumor protein (TCTP) is a multifunctional and highly conserved protein from yeast to humans. Recently, its role in non-selective autophagy has been reported with controversial results in mammalian and human cells. Herein we examine the effect of Mmi1, the yeast ortholog of TCTP, on non-selective autophagy in budding yeast Saccharomyces cerevisiae, a well-established model system to monitor autophagy. We induced autophagy by nitrogen starvation or rapamycin addition and measured autophagy by using the Pho8?60 and GFP-Atg8 processing assays in WT, mmi1?, and in autophagy-deficient strains atg8? or atg1?. Our results demonstrate that Mmi1 does not affect basal or nitrogen starvation-induced autophagy. However, an increased rapamycin-induced autophagy is detected in mmi1? strain when the cells enter the post-diauxic growth phase, and this phenotype can be rescued by inserted wild-type MMI1 gene. Further, the mmi1? cells exhibit significantly lower amounts of reactive oxygen species (ROS) in the post-diauxic growth phase compared to WT cells. In summary, our study suggests that Mmi1 negatively affects rapamycin-induced autophagy in the post-diauxic growth phase and supports the role of Mmi1/TCTP as a negative autophagy regulator in eukaryotic cells.

SUBMITTER: Vojtova J

PROVIDER: S-EPMC7017036 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Mmi1, the Yeast Ortholog of Mammalian Translationally Controlled Tumor Protein (TCTP), Negatively Affects Rapamycin-Induced Autophagy in Post-Diauxic Growth Phase.

Vojtova Jana J Hasek Jiri J

Cells 20200107 1

Translationally controlled tumor protein (TCTP) is a multifunctional and highly conserved protein from yeast to humans. Recently, its role in non-selective autophagy has been reported with controversial results in mammalian and human cells. Herein we examine the effect of Mmi1, the yeast ortholog of TCTP, on non-selective autophagy in budding yeast <i>Saccharomyces cerevisiae</i>, a well-established model system to monitor autophagy. We induced autophagy by nitrogen starvation or rapamycin addit ...[more]

PMID: 31936125

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Project description:BackgroundTranslationally controlled tumour protein (TCTP), a well known protein of the animal kingdom, was shown to be a Ca(2+)-binding protein with important functions in many different cellular processes (e.g. protection against stress and apoptosis, cell growth, cell cycle progression, and microtubule organization). However, only little is known about TCTP in plants. Transcript and protein levels of plant TCTPs were shown to be altered by various stress conditions (e.g. cold, salt, draught, aluminium, and pathogen infection), and Arabidopsis thaliana TCTP (AtTCTP) was described as an important regulator of growth. The aim of this study was to further characterize plant TCTP relating to one of its major functions in animals: the protection against cell death.ResultsWe used two different activators of programmed cell death (PCD) in plants: the mammalian pro-apoptotic protein BAX and tunicamycin, an inhibitor of glycosylation and trigger of unfolded protein response (UPR). Over-expression of AtTCTP significantly decreased cell death in tobacco leaf discs in both studies. A (45)Ca overlay assay showed AtTCTP to be a Ca(2+)-binding protein and localization experiments revealed cytosolic distribution of AtTCTP-GFP in Arabidopsis seedlings.ConclusionsOur study showed cytoprotective effects of plant TCTP for the first time. Furthermore, we showed the ability of AtTCTP to bind to Ca(2+) and its cytosolic distribution within the cell. If these results are combined, two putative modes of action can be assumed: 1) AtTCTP acts as Ca(2+) sequester, preventing PCD by reducing cytosolic Ca(2+) levels as described for animals. 2) AtTCTP could directly or indirectly interact with other cytosolic or membrane-bound proteins of the cell death machinery, thereby inhibiting cell death progression. As no homologous proteins of the anti-apoptotic machinery of animals were found in plants, and functional homologues still remain to be elucidated, future work will provide more insight.

Dataset Information

Mmi1, the Yeast Ortholog of Mammalian Translationally Controlled Tumor Protein (TCTP), Negatively Affects Rapamycin-Induced Autophagy in Post-Diauxic Growth Phase.

Publications

Mmi1, the Yeast Ortholog of Mammalian Translationally Controlled Tumor Protein (TCTP), Negatively Affects Rapamycin-Induced Autophagy in Post-Diauxic Growth Phase.

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