Transcriptional and post-transcriptional regulation of autophagy in the yeast Saccharomyces cerevisiae

Delorme-Axford, Elizabeth; Klionsky, Daniel J.

doi:10.1074/jbc.r117.804641

Cited by 58 publications

(50 citation statements)

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“…This process continued until the vacuole filled such cells, while their fluorescence and then their nucleus completely vanished. These features suggest that some cells might attempt surviving by autophagy ( 50 , 51 ), until they succumb to cell death. Taken together with the stable bimodal gene expression histograms for cooled and heated NF0 cells, we concluded that cooled and heated yeast cells segregate into two phenotypically distinct subpopulations ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Multiscale effects of heating and cooling on genes and gene networks

Charlebois

Hauser

Marshall

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceFluctuating environments such as changes in ambient temperature represent a fundamental challenge to life. Cells must protect gene networks that protect them from such stresses, making it difficult to understand how temperature affects gene network function in general. Here, we focus on single genes and small synthetic network modules to reveal four key effects of nonoptimal temperatures at different biological scales: (i) a cell fate choice between arrest and resistance, (ii) slower growth rates, (iii) Arrhenius reaction rates, and (iv) protein structure changes. We develop a multiscale computational modeling framework that captures and predicts all of these effects. These findings promote our understanding of how temperature affects living systems and enables more robust cellular engineering for real-world applications.

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Section: Resultsmentioning

confidence: 99%

Multiscale effects of heating and cooling on genes and gene networks

Charlebois

Hauser

Marshall

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…The myriad of mechanisms that are exerted by the cell to control the induction and magnitude of the autophagy response, along with the high level of pathway conservation throughout eukaryotes, highlight how important this process is for maintaining cellular integrity and survival during stress. Although here we focus mainly on post‐transcriptional regulation by RNA decay, cells also utilize multiple layers of regulation through transcriptional (Bartholomew et al, ; Bernard, Jin, Gonzalez‐Rodriguez, et al, ; Bernard, Jin, Xu, & Klionsky, ; Jin et al, ), translational (Lubas et al, ; Rojas‐Rios et al, ; Wek, Zhu, & Wek, ) and post‐translational (Feng et al, ; Mao et al, ; Russell et al, ) mechanisms (reviewed in Delorme‐Axford & Klionsky, ; Feng, Yao, & Klionsky, ; Popelka & Klionsky, ). Despite the immense progress that has been achieved towards understanding how cells control autophagy, many questions remain.…”

Section: Discussionmentioning

confidence: 99%

“…The yeast kinase Rim15 positively regulates autophagy through the integration of signals from two major nutrient sensing pathways—TOR and protein kinase A (Delorme‐Axford & Klionsky, ; Reggiori & Klionsky, ; Yorimitsu, Zaman, Broach, & Klionsky, ). Rim15 phosphorylates at least two mediators of ATG gene repression in yeast—Ume6 (Bartholomew et al, ) and Rph1 (Bernard et al, ).…”

Section: Autophagy Regulation By Rna Decaymentioning

confidence: 99%

“…Under nutrient‐replete conditions, Dcp2 is phosphorylated by TORC1 in C. neoformans , driving its regulation of (at least) ATG8 mRNA by recruitment to the decapping machinery (Hu et al, ). In this mechanism, TORC1 negatively regulates the translation of ATG transcripts under nutrient‐replete conditions, but promotes the translation of the bulk of cellular transcripts (Delorme‐Axford & Klionsky, ). A homologous mechanism was identified in mammalian cells wherein MTOR phosphorylates DDX6 (Hu et al, ).…”

Section: Autophagy Regulation By Rna Decaymentioning

confidence: 99%

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On the edge of degradation: Autophagy regulation by RNA decay

Delorme-Axford

Klionsky

2018

WIREs RNA

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Cells must dynamically adapt to altered environmental conditions, particularly during times of stress, to ensure their ability to function effectively and survive. The macroautophagy/autophagy pathway is highly conserved across eukaryotic cells and promotes cell survival during stressful conditions. In general, basal autophagy occurs at a low level to sustain cellular homeostasis and metabolism. However, autophagy is robustly upregulated in response to nutrient deprivation, pathogen infection and increased accumulation of potentially toxic protein aggregates and superfluous organelles. Within the cell, RNA decay maintains quality control to remove aberrant transcripts and regulate appropriate levels of gene expression. Recent evidence has identified components of the cellular mRNA decay machinery as novel regulators of autophagy. Here, we review current findings that demonstrate how autophagy is modulated through RNA decay. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability K E Y W O R D S Dcp2, DDX6, Dhh1, mRNA decay, RNA degradation, vacuole, Xrn1/XRN1, yeast 1 | INTRODUCTION 1.1 | OverviewWhen encountering altered environments and fluctuating nutrient conditions, cells must respond and adapt through mechanisms that support their survival. Autophagy is a precisely controlled catabolic process of cellular "self-eating" that is highly conserved across eukaryotes (from yeast to human). Starvation, pathogen infection and/or the accumulation of damaged or superfluous organelles can activate the autophagy pathway, which enables eukaryotic cells to function and survive amid stress conditions. Autophagy also removes harmful cellular material, while at the same time providing a source of macromolecules to sustain cellular metabolism during low-energy periods. The de novo formation of the sequestering phagophore, which matures into a double-membrane autophagosome is the characteristic morphological feature of autophagy. At present, 42 autophagy-related (ATG) genes have been identified in fungi; many of these genes have homologs or at least functional counterparts in higher eukaryotes. Autophagy is primarily a degradative pathway requiring the vacuole (in yeast or plants) or lysosomes (in metazoans) for the breakdown of sequestered cargo. However, the biosynthetic cytoplasm-to-vacuole targeting (Cvt) pathway utilizes most of Abbreviations: ATG, autophagy-related; CPA, cleavage and polyadenylation; Cvt, cytoplasm-to-vacuole targeting; GABARAP, GABA type A receptorassociated protein; MAP1LC3/ LC3, microtubule associated protein 1 light chain 3; miRNA, microRNA; mRNA, messenger RNA; MTOR, mechanistic target of rapamycin kinase;

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“…In short, autophagy under normal conditions occurs at a low intensity; however, this process is clearly enhanced as a result of various types of abiotic and biotic stresses mboxciteB29-ijms-741503,B129-ijms-741503,B130-ijms-741503,B131-ijms-741503. In yeast, the main factors that increase the intensity of autophagy are carbon, nitrogen and phosphate starvation [24,129]. In plants, it is known that carbon or nitrogen starvation significantly increases the intensity of autophagy [7,24,29,36,132,133].…”

Section: Regulation Of Autophagic Body Degradationmentioning

confidence: 99%

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

Stefaniak

Wojtyla

Pietrowska‐Borek

et al. 2020

IJMS

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Autophagy is an evolutionarily conserved process that occurs in yeast, plants, and animals. Despite many years of research, some aspects of autophagy are still not fully explained. This mostly concerns the final stages of autophagy, which have not received as much interest from the scientific community as the initial stages of this process. The final stages of autophagy that we take into consideration in this review include the formation and degradation of the autophagic bodies as well as the efflux of metabolites from the vacuole to the cytoplasm. The autophagic bodies are formed through the fusion of an autophagosome and vacuole during macroautophagy and by vacuolar membrane invagination or protrusion during microautophagy. Then they are rapidly degraded by vacuolar lytic enzymes, and products of the degradation are reused. In this paper, we summarize the available information on the trafficking of the autophagosome towards the vacuole, the fusion of the autophagosome with the vacuole, the formation and decomposition of autophagic bodies inside the vacuole, and the efflux of metabolites to the cytoplasm. Special attention is given to the formation and degradation of autophagic bodies and metabolite salvage in plant cells.

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Transcriptional and post-transcriptional regulation of autophagy in the yeast Saccharomyces cerevisiae

Cited by 58 publications

References 100 publications

Multiscale effects of heating and cooling on genes and gene networks

Multiscale effects of heating and cooling on genes and gene networks

On the edge of degradation: Autophagy regulation by RNA decay

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

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