Fission yeast autophagy induced by nitrogen starvation generates a nitrogen source that drives adaptation processes

Kohda, Toshiki A.; Tanaka, Kayoko; Konomi, Mami; Sato, Mamiko; Osumi, Masako; Yamamoto, Masayuki

doi:10.1111/j.1365-2443.2007.01041.x

Cited by 96 publications

(124 citation statements)

References 49 publications

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“…Therefore, autophagy is also required for long-term survival in G0, though the degree is much less than proteasome function. This is consistent with the previous report (31).…”

Section: Resultssupporting

confidence: 83%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

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

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Regulations of proliferation and quiescence in response to nutritional cues are important for medicine and basic biology. The fission yeast Schizosaccharomyces pombe serves as a model, owing to the shift of proliferating cells to the metabolically active quiescence (designate G0 phase hereafter) by responding to low nitrogen source. S. pombe G0 phase cells keep alive for months without growth and division. Nitrogen replenishment reinstates vegetative proliferation phase (designate VEG). Some 40 genes required for G0 maintenance were identified, but many more remain to be identified. We here show, using mutants, that the proteasome is required for maintaining G0 quiescence. Functional outcomes of proteasome in G0 and VEG phases appear to be distinct. Upon proteasome dysfunction, a number of antioxidant proteins and compounds responsive to ROS (reactive oxygen species) are produced. In addition, autophagy-mediated destruction of mitochondria occurs, which suppresses the loss of viability by eliminating ROS-generating mitochondria. These defensive responses are found in G0 but not in VEG, suggesting that the main function of proteasome in G0 phase homeostasis is to minimize ROS. Proteasome and autophagy are thus collaborative to support the lifespan of S. pombe G0 phase.cell cycle | cellular quiescence | proteolysis | mitochondria

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“…Therefore, autophagy is also required for long-term survival in G0, though the degree is much less than proteasome function. This is consistent with the previous report (31).…”

Section: Resultssupporting

confidence: 83%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

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

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“…In fission yeast, it is demonstrated that autophagy contributes to the maintenance of cell viability upon nitrogen depletion (Kohda et al 2007). These reports prompted us to compare the growth of wildtype, Dtsc2, and Dnpr2 cells harboring the leu1-32 mutation upon nitrogen deprivation on YES plates.…”

Section: The Role Of Npr2 In the Regulation Of Autophagymentioning

confidence: 99%

TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast

Liu

Zhang

et al. 2013

Genetics

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The target of rapamycin (TOR) is a highly conserved protein kinase that regulates cell growth and metabolism. Here we performed a genome-wide screen to identify negative regulators of TOR complex 1 (TORC1) in Schizosaccharomyces pombe by isolating mutants that phenocopy Dtsc2, in which TORC1 signaling is known to be up-regulated. We discovered that Dnpr2 displayed similar phenotypes to Dtsc2 in terms of amino acid uptake defects and mislocalization of the Cat1 permease. However, Dnpr2 and Dtsc2 clearly showed different phenotypes in terms of rapamycin supersensitivity and Isp5 transcription upon various treatments. Furthermore, we showed that Tor2 controls amino acid homeostasis at the transcriptional and post-transcriptional levels. Our data reveal that both Npr2 and Tsc2 negatively regulate TORC1 signaling, and Npr2, but not Tsc2, may be involved in the feedback loop of a nutrient-sensing pathway.T HE target of rapamycin (TOR) plays vitally important roles in regulating cell growth and metabolism. TOR interacts with several proteins to form two structurally and functionally distinct complexes named TOR complex 1 (TORC1) and 2 (TORC2) Sabatini 2009, 2012). In response to environmental cues, TORC1 controls cell growth and differentiation by coordinating diverse cellular processes including transcription, translation, and autophagy. Research on TORC1 has generated a model of the complex TOR signaling network (Huang and Manning 2009;Orlova and Crino 2010;Laplante and Sabatini 2012). In the regulation of TORC1 signaling, four major signals have been identified, namely growth factors (insulin, IGF, etc.), energy status (AMP/ATP ratio), oxygen levels, and nutrients (amino acids) Sabatini 2009, 2012). In mammals, the tuberous sclerosis complex 1 and 2 (TSC1-TSC2) serves as a key point of signal integration. The growth factors stimulate TORC1 signaling via PI3K-Akt/ PKB-mediated phosphoinhibition of TSC2 (Inoki et al. 2002;Manning et al. 2002). The energy starvation inhibits TORC1 signaling via AMPK-dependent phosphoactivation of TSC2 (Inoki et al. 2003). Then, TSC2 negatively regulates TORC1 activity by converting GTP-bound Rheb (Ras homolog enriched in brain) into its inactive GDP-bound state (Inoki et al. 2003;Tee et al. 2003). The amino acids, in particular the branched-chain amino acid leucine, positively regulate TORC1. The TORC1 signaling remains sensitive to amino acid deprivation in TSC2 2/2 cells (Nobukuni et al. 2005), indicating that the activation of TORC1 by amino acids is independent of TSC2. Recently, it was demonstrated that TORC1 responds to amino acid availability via mechanisms involving Rag GTPases (Sancak et al. 2008). In the presence of amino acids, the Rag GTPases interact with TORC1, thereby promoting the translocation of TORC1 to the lysosomal membranes and facilitating Rheb's activation of TORC1 (Sancak et al. 2010).In budding yeast Saccharomyces cerevisiae, TOR1 and TOR2 genes were originally identified as the targets of rapamycin, and mutations in TOR1 or TOR2 genes confer resi...

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“…23 Although GFP release from Atg8-GFP is a good measure of autophagic activity, this assay does not provide an insight into how dysfunctional autophagy affects the long-term survival of S. pombe. Hence, we next assessed the potential role of SpAtg10 in the long-term survival of nitrogen-starved cells.…”

Section: Resultsmentioning

confidence: 99%

An Atg10-like E2 enzyme is essential for cell cycle progression but not autophagy inSchizosaccharomyces pombe

Flanagan

Whitehall²,

Morgan³

2013

Cell Cycle

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Fission yeast autophagy induced by nitrogen starvation generates a nitrogen source that drives adaptation processes

Cited by 96 publications

References 49 publications

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast

An Atg10-like E2 enzyme is essential for cell cycle progression but not autophagy inSchizosaccharomyces pombe

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