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 Pho8Δ60 and GFP-Atg8 processing assays in WT, mmi1Δ, and in autophagy-deficient strains atg8Δ or atg1Δ. Our results demonstrate that Mmi1 does not affect basal or nitrogen starvation-induced autophagy. However, an increased rapamycin-induced autophagy is detected in mmi1Δ strain when the cells enter the post-diauxic growth phase, and this phenotype can be rescued by inserted wild-type MMI1 gene. Further, the mmi1Δ 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.

Dysregulation of TCTP in Biological Processes and Diseases

“…Both these studies demonstrated that TCTP is indeed able to modulate autophagy, however, the actual outcome is very much dependent on the precise cell physiologic conditions. Consistent with this, another paper on TCTP regulation of autophagy, published in this Special Issue, observed that TCTP negatively affects rapamycin-induced autophagy in the post-diauxic growth phase in yeast, but not autophagy induced by nitrogen starvation [54].…”

Biological role and expression of translationally controlled tumor protein (TCTP) in tumorigenesis and development and its potential for targeted tumor therapy

“…Early studies suggested that TCTP promoted autophagy [ 105 ]. Whereas, most subsequent research has indicated that TCTP may restrain cellular autophagy [ 106 , 107 ]. A study has demonstrated that the downregulation of TCTP expression facilitates the formation and maturation of autophagosomes, as observed through the formation of LC3 puncta and co-localization of LC3 with the lysosomal marker LAMP1 [ 106 ].…”

Role of TCTP in Cell Biological and Disease Processes

“…Therefore, we welcomed the review article by Kyunglim Lee and colleagues [ 6 ], which discussed these aspects of TCTP function, in relation to its role in tumorigenesis. An original study by Vojtova and Hasek [ 7 ] investigated the importance of Mmi1, the yeast orthologue of mammalian TCTP, in non-selective autophagy in the yeast S. cerevisiae . They found that Mmi1 negatively affects rapamycin-induced autophagy, whereas it had no effect on nitrogen starvation-induced autophagy.…”