Atg1-dependent phosphorylation of Vps34 is required for dynamic regulation of the phagophore assembly site and autophagy in <i>Saccharomyces cerevisiae</i>

Lee, Yongook; Kim, Bongkeun; Jang, Hae-Soo; Huh, Won-Ki

doi:10.1080/15548627.2023.2182478

Cited by 10 publications

(4 citation statements)

References 72 publications

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“…This Vps34 phosphorylation may be involved in regulating the associations of PI3KCI with the Atg1 complex and Atg9. A recent study showed that Atg1 directly phosphorylates Vps34 in vitro ( Lee et al, 2023 ). Atg1 can also phosphorylate other PI3KCI subunits (Vps30 and Atg38), Atg1 complex subunits (Atg13, Atg29, and Atg1 itself), and Atg9 ( Papinski et al, 2014 ; Kamber et al, 2015 ; Hu et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The Atg1 complex, Atg9, and Vac8 recruit PI3K complex I to the pre-autophagosomal structure

Hitomi

Kotani

Noda

et al. 2023

Journal of Cell Biology

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In macroautophagy, cellular components are sequestered within autophagosomes and transported to lysosomes/vacuoles for degradation. Although phosphatidylinositol 3-kinase complex I (PI3KCI) plays a pivotal role in the regulation of autophagosome biogenesis, little is known about how this complex localizes to the pre-autophagosomal structure (PAS). In Saccharomyces cerevisiae, PI3KCI is composed of PI3K Vps34 and conserved subunits Vps15, Vps30, Atg14, and Atg38. In this study, we discover that PI3KCI interacts with the vacuolar membrane anchor Vac8, the PAS scaffold Atg1 complex, and the pre-autophagosomal vesicle component Atg9 via the Atg14 C-terminal region, the Atg38 C-terminal region, and the Vps30 BARA domain, respectively. While the Atg14–Vac8 interaction is constitutive, the Atg38–Atg1 complex interaction and the Vps30–Atg9 interaction are enhanced upon macroautophagy induction depending on Atg1 kinase activity. These interactions cooperate to target PI3KCI to the PAS. These findings provide a molecular basis for PAS targeting of PI3KCI during autophagosome biogenesis.

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Section: Discussionmentioning

confidence: 99%

The Atg1 complex, Atg9, and Vac8 recruit PI3K complex I to the pre-autophagosomal structure

Hitomi

Kotani

Noda

et al. 2023

Journal of Cell Biology

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“…Atg1 phosphorylates the Atg4 protease, keeping it inactive and preventing the premature release of Atg8 from autophagic membranes, and Ykt6 keeps this SNARE in an inactive state and so regulates the autophagosome-vacuole fusion [ 53 , 54 ]. Another Atg1 target is Vps34, a class III phosphatidylinositol 3-kinase whose phosphorylation is important for full autophagy activation and cell survival [ 55 ]. Vps34 was mislocalized in mutants of the Nem1/Spo7-Pah1 axis but localized at the right compartments after rapamycin treatment, suggesting that the Nem1/Spo7 complex supports autophagy induction after TORC1 inactivation by nutrient starvation, probably via membrane synthesis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy

Caraba,

Stirpe,

Palermo

et al. 2023

IJMS

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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 an Lsm4 null strain S. cerevisiae (Sclsm4Δ1) restored cell viability. Nevertheless, in this transformed strain, we observed some phenotypes that are typical markers of regulated cell death, reactive oxygen species (ROS), and oxidated RNA accumulation. In this paper, we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers on cells the same phenotypes observed with the K. lactis lsm4Δ1 gene. Up until now, there was no evidence of the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4Δ1 mutant showed a block in the autophagic process and was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and aging, the Sclsm4Δ1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in a later step of the autophagy process.

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“…Recruitment of the Atg machinery to the PAS, its assembly, and its activation are orchestrated by protein phosphorylations [17,18,[44][45][46] and PtdIns3P biosynthesis [47]. As a result, it is not unexpected that experimental evidence points to the inactivation of kinases and activation of phosphatases as one of the major mechanisms for the Atg machinery disengagement and release (Fig.…”

Section: Autophagosome Maturationmentioning

confidence: 99%

Phagophore closure, autophagosome maturation and autophagosome fusion during macroautophagy in the yeast Saccharomyces cerevisiae

Kraft

Reggiori

2023

FEBS Letters

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Macroautophagy, hereafter referred to as autophagy, is a complex process in which multiple membrane‐remodeling events lead to the formation of a cisterna known as the phagophore, which then expands and closes into a double‐membrane vesicle termed the autophagosome. During the past decade, enormous progress has been made in understanding the molecular function of the autophagy‐related proteins and their role in generating these phagophores. In this Review, we discuss the current understanding of three membrane remodeling steps in autophagy that remain to be largely characterized; namely, the closure of phagophores, the maturation of the resulting autophagosomes into fusion‐competent vesicles, and their fusion with vacuoles/lysosomes. Our review will mainly focus on the yeast Saccharomyces cerevisiae, which has been the leading model system for the study of molecular events in autophagy and has led to the discovery of the major mechanistic concepts, which have been found to be mostly conserved in higher eukaryotes.

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Atg1-dependent phosphorylation of Vps34 is required for dynamic regulation of the phagophore assembly site and autophagy in Saccharomyces cerevisiae

Cited by 10 publications

References 72 publications

The Atg1 complex, Atg9, and Vac8 recruit PI3K complex I to the pre-autophagosomal structure

The Atg1 complex, Atg9, and Vac8 recruit PI3K complex I to the pre-autophagosomal structure

Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy

Phagophore closure, autophagosome maturation and autophagosome fusion during macroautophagy in the yeast Saccharomyces cerevisiae

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