Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Yeast lsm Pro-Apoptotic Mutants Show Defects in Autophagy Induction

Version 1 : Received: 19 July 2023 / Approved: 19 July 2023 / Online: 20 July 2023 (02:51:12 CEST)

A peer-reviewed article of this Preprint also exists.

Caraba, B.; Stirpe, M.; Palermo, V.; Vaccher, U.; Bianchi, M.M.; Falcone, C.; Mazzoni, C. Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy. Int. J. Mol. Sci. 2023, 24, 13708. Caraba, B.; Stirpe, M.; Palermo, V.; Vaccher, U.; Bianchi, M.M.; Falcone, C.; Mazzoni, C. Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy. Int. J. Mol. Sci. 2023, 24, 13708.

Abstract

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability and translation. In previous papers we reported that the expression in S. cerevisiae of the K. lactis Lsm4 gene lacking the C-terminal Q/N-rich domain in a Lsm4 null strain S. cerevisiae (Sclsm4D1) restored cell viability. Nevertheless, in this transformed strain we observed some phenotypes which are typical markers of regulated cell death, Reactive Oxygen Species and oxidated RNA accumulation. In this paper we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers to cells the same phenotypes observed with the K.lactis LSM4D1 gene. Up to now there was no evidence on the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4D1 mutant showed defects in the induction of autophagy and it was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and ageing, the Sclsm4D1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in Phagophore Assembly Site (PAS) processing and/or vacuolar autophagosome internalization

Keywords

Autophagy; Ageing; LSM4; Yeast

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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