Atg22 Recycles Amino Acids to Link the Degradative and Recycling Functions of Autophagy

Yang, Zhifen; Huang, Ju; Geng, Jiefei; Nair, Usha; Klionsky, Daniel J.

doi:10.1091/mbc.e06-06-0479

Cited by 237 publications

(200 citation statements)

References 29 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the atg22D mutant accumulated both the full-length fusion protein and the isolated GFP moiety, consistent with the results of atg22D in budding yeast (Fig. 1a) (Yang et al, 2006). In budding yeast, Atg22p was reported to be a vacuolar membrane amino acid transporter, which could mediate amino acid efflux during autophagy.…”

Section: Autophagy Deficiency In Atg Mutants In Fission Yeastsupporting

confidence: 87%

“…Yang et al (2006) showed that atg22p is also a vacuolar effluxer of leucine and other amino acids, functioning redundantly with Avt3p and Avt4p, and these proteins are partially required to supply amino acids for de novo protein synthesis after the autophagic process. The fission yeast genome database revealed the existence of two AVT homologues, SPAC3H1.09C and SPBC1685.07C, the encoded proteins of which share 63 % and 67 % similarity with budding yeast Avt3p and Avt5p, respectively.…”

Section: Rescue Of Sporulation Deficiency By Amino Acid Supplementatimentioning

confidence: 99%

See 1 more Smart Citation

Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation

et al. 2009

View full text Add to dashboard Cite

Autophagy is triggered when organisms sense radical environmental changes, including nutritional starvation. During autophagy, cytoplasmic components, including organelles, are enclosed within autophagosomes and are degraded upon lysosome-vacuole fusion. In this study, we show that processing of GFP-tagged Atg8 can serve as a marker for autophagy in the fission yeast Schizosaccharomyces pombe. Using this marker, 13 Atg homologues were also found to be required for autophagy in fission yeast. In budding yeast, autophagy-deficient mutants are known to be sterile, whereas in fission yeast we found that up to 30 % of autophagy-defective cells with amino acid auxotrophy were able to recover sporulation when an excess of required amino acids was supplied. Furthermore, we found that approximately 15 % of the autophagydefective cells were also able to sporulate when a prototrophic strain was subjected to nitrogen starvation, which suggested that fission yeast may store sufficient intracellular nitrogen to allow partial sporulation under nitrogen-limiting conditions, although the majority of the nitrogen source is supplied by autophagy. Monitoring of the sporulation process revealed that the process was blocked non-specifically at various stages in the atg1D and atg12D mutants, possibly due to a shortage of amino acids. Taking advantage of this partial sporulation ability of fission yeast, we sought evidence for the existence of a recycling system for nitrogen sources during starvation. INTRODUCTIONAutophagy is a degradative pathway conserved among eukaryotic cells, and is responsible for turnover of damaged organelles and long-lived proteins. When living organisms are exposed to radical environmental changes such as nutrient starvation, differentiation or development, autophagy is rapidly induced and inner cell components are reorganized. In the budding yeast Saccharomyces cerevisiae, autophagy is triggered by starvation for nitrogen or carbon, after which endogenous proteins and organelles are enclosed within isolated membranes called autophagosomes. The outer membrane of the autophagosome then fuses with the vacuole, allowing the contents of the autophagosome, designated autophagic bodies, to be released and degraded in the vacuole. The molecular mechanisms involved in the process of autophagy have been subjected to detailed genetic analysis and more than 20 AuTophaGy-related (ATG) genes essential for autophagy have been identified in Sac. cerevisiae Kamada et al., 2000;Mizushima et al., 1998).One of the most striking findings with respect to function of the Atg proteins was the discovery of two ubiquitin-like conjugation systems involving Atg12p and Atg8p (Ohsumi, 2001). Atg12p, which has no apparent homology to ubiquitin, covalently attaches to Atg5p in a manner analogous to ubiquitination, and then forms a complex with Atg16p. Atg8p also lacks similarity to ubiquitin, but Abbreviations: DAPI, 49,6-diamidino-2-phenylindole; DIC, differential interference contrast; FSM, forespore membrane.Two supplementary tables a...

show abstract

Section: Autophagy Deficiency In Atg Mutants In Fission Yeastsupporting

confidence: 87%

Section: Rescue Of Sporulation Deficiency By Amino Acid Supplementatimentioning

confidence: 99%

Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…We thus asked if Rot1 chaperones proteins that are involved in this cellular event. Atg22 is a polytopic membrane protein and probably acts as an amino acid permease in the vacuolar membrane (Yang et al, 2006). We found that the cellular level of Atg22 was decreased by the rot1-2 mutation at 37°C ( Figure 6D).…”

Section: Rot1 May Chaperone Kre5 and Atg22mentioning

confidence: 84%

Saccharomyces cerevisiaeRot1 Is an Essential Molecular Chaperone in the Endoplasmic Reticulum

Takeuchi

Kohno

2008

MBoC

View full text Add to dashboard Cite

Molecular chaperones prevent aggregation of denatured proteins in vitro and are thought to support folding of diverse proteins in vivo. Chaperones may have some selectivity for their substrate proteins, but knowledge of particular in vivo substrates is still poor. We here show that yeast Rot1, an essential, type-I ER membrane protein functions as a chaperone. Recombinant Rot1 exhibited antiaggregation activity in vitro, which was partly impaired by a temperature-sensitive rot1-2 mutation. In vivo, the rot1-2 mutation caused accelerated degradation of five proteins in the secretory pathway via ER-associated degradation, resulting in a decrease in their cellular levels. Furthermore, we demonstrate a physical and probably transient interaction of Rot1 with four of these proteins. Collectively, these results indicate that Rot1 functions as a chaperone in vivo supporting the folding of those proteins. Their folding also requires BiP, and one of these proteins was simultaneously associated with both Rot1 and BiP, suggesting that they can cooperate to facilitate protein folding. The Rot1-dependent proteins include a soluble, type I and II, and polytopic membrane proteins, and they do not share structural similarities. In addition, their dependency on Rot1 appeared different. We therefore propose that Rot1 is a general chaperone with some substrate specificity.

show abstract

“…The final stage of autophagy is the efflux of metabolites generated by the lysosomal degradation of macromolecules into the cytosol (reviewed in [95]). Atg22 has recently been identified as a permease that recycles amino acids from the vacuole in S. cerevisiae [96].…”

Section: Acidification and Degradationmentioning

confidence: 99%

Overview of macroautophagy regulation in mammalian cells

et al. 2010

View full text Add to dashboard Cite

Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGyrelated genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of autophagy is now better understood because of the discovery that the activity of Atg complexes is targeted by protein kinases, and owing to the importance of nuclear regulation via transcription factors in regulating the expression of autophagy genes.

show abstract

Atg22 Recycles Amino Acids to Link the Degradative and Recycling Functions of Autophagy

Cited by 237 publications

References 29 publications

Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation

Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation

Saccharomyces cerevisiaeRot1 Is an Essential Molecular Chaperone in the Endoplasmic Reticulum

Overview of macroautophagy regulation in mammalian cells

Contact Info

Product

Resources

About