Tor-Mediated Induction of Autophagy via an Apg1 Protein Kinase Complex

By Y. Kamada, T. Funakoshi, T. Shintani, K. Nagano, M. Ohsumi, Y. Ohsumi. Journal of Cell Biology, 2000

1,226 citations recorded by the source corpus.

Autophagy is a membrane trafficking to vacuole/lysosome induced by nutrient starvation. In Saccharomyces cerevisiae, Tor protein, a phosphatidylinositol kinase-related kinase, is involved in the repression of autophagy induction by a largely unknown mechanism. Here, we show that the protein kinase activity of Apg1 is enhanced by starvation or rapamycin treatment. In addition, we have also found that Apg13, which binds to and activates Apg1, is hyperphosphorylated in a Tor-dependent manner, reducing its affinity to Apg1. This Apg1–Apg13 association is required for autophagy, but not for the cytoplasm-to-vacuole targeting (Cvt) pathway, another vesicular transport mechanism in which factors essential for autophagy (Apg proteins) are also employed under vegetative growth conditions. Finally, other Apg1-associating proteins, such as Apg17 and Cvt9, are shown to function specifically in autophagy or the Cvt pathway, respectively, suggesting that the Apg1 complex plays an important role in switching between two distinct vesicular transport systems in a nutrient-dependent manner.

Subfields: Cell Biology, Epidemiology

View Paper: https://www.semanticscholar.org/paper/7552f5796b832ef8fec202e4a275889d60ce019f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

In Epidemiology

Citations in the corpus

Autophagy as a cell death and tumor suppressor mechanism (2004, background): “(Kamada et al., 2000; Scott et al., 2000).”
TOR signaling in growth and metabolism. (2006, background): “In yeast, TOR negatively controls macroautophagy via inhibition of the protein kinase ATG1 that mediates an early activation step in the autophagic process (Kamada et al., 2000).”
The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism (2011, background): “In budding yeast, the Atg1 complex is inhibited by the TOR–Raptor complex (target of rapamycin complex 1; TORC1”
Autophagy and autophagy-related proteins in cancer (2020, background): “binds to both Atg1 and Atg17 and the Atg17-Atg13 complex formation plays an important role in normal autophagosome formation via binding to and activating the Atg1 kinase [33, 93, 96, 101, 102].”
Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. (2007, neutral): “Activated TOR inhibits Atg1 (Kamada et al., 2000), a critical positive regulator of autophagy.”
“Sleeping Beauty”: Quiescence in Saccharomyces cerevisiae (2004, background): “Apg1p-Apg13p association is required for starvation-induced autophagy but not for the Cvt pathway (74, 76).”
Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease (2008, background): “Atg1p activation involves rapid dephosphorylation of Atg13p, which facilitates its interaction with Atg1p and Atg17p (ref”
Guidelines for the use and interpretation of assays for monitoring autophagy (2012, background): “Currently, the most commonly used inducer of autophagy is rapamycin, an allosteric inhibitor of TORC1, although one caution is that MTOR is a major regulatory protein that is part of the insulin signaling pathway, and it controls processes other than autophagy, so that rapamycin will ultimately affe”
The environmental stress response: a common yeast response to diverse environmental stresses (2003, background): “To prevent such widespread internal damage, the cell has evolved to initiate the ESR in response to diverse signals of cellular stress in order to protect and maintain these critical features of the internal system.”
Hierarchy of Atg proteins in pre‐autophagosomal structure organization (2007, background): “This assumption is consistent with the finding that Atg11p facilitates the recruitment of Atg1p, Atg2p, Atg8p and Atg20p to a punctate structure under growth conditions (Shintani & Klionsky 2004b).”
Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “Many reports hypothesize that inhibition of mTORC1 contributes to the manifestation of these stress-related phenotypes (Khamzina et al., 2005; Kimball et al., 2000; Lang et al., 2010; McGhee et al., 2009).”
Role and regulation of starvation-induced autophagy in the Drosophila fat body. (2004, methodology): “activity is regulated by TOR signaling in yeast (Kamada et al., 2000).”
An Overview of the Molecular Mechanism of Autophagy (2009, background): “The kinase activity of Atg1 is essential for both autophagy and the Cvt pathway, although a higher level of kinase activity appears to be needed for the Cvt pathway (Kamada et al. 2000; Kabeya et al. 2005; Cheong et al. 2008; Abeliovich et al. 2003).”
Autophagy in the Cellular Energetic Balance (2011, neutral): “In yeast, activation of TORC hyperphosphorylates Atg13, preventing its interaction with Atg1 (Kamada et al., 2000).”
Autophagy: molecular machinery for self-eating (2005, background): “In yeast, Tor controls the phosphorylation state of Atg13, one of the proteins required for autophagy (Figure 2).(33,34) In nutrient-rich conditions, Atg13 is highly phosphorylated and has a lower affinity for Atg1 kinase; in this situation autophagy is repressed.”
Deacetylation of nuclear LC3 drives autophagy initiation under starvation. (2015, background): “Various signaling pathwaysare known to trigger autophagy during starvation (Kamada et al., 2000; Kim et al., 2011; Lin et al., 2012; Wei et al., 2013), but exactly what occurs mechanistically to enable LC3 to interact with Atg7 and other autophagy effectors to thereafter initiate autophagosomebiogen”