Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity
Open accessAbstract
Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15–Vps34 and Atg14–Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15–Vps34 and Atg14–Vps30 subcomplexes to facilitate complex I formation.
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NRBF2 is a novel component of the PtdIns3K complex and associates with ATG14 in both mammalian cells and yeast.
“NRBF2 is a novel component of the PtdIns3K complex, and associates with ATG14 in both mammalian cells [25][26][27][28] and in yeast (where it is named Atg38).29”
From NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models (2017) · cites this paper as [29]
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- Authors
- Araki, Y., Ku, W.-C., Akioka, M., May, A. I., Hayashi, Y., Arisaka, F., Ishihama, Y., & Ohsumi, Y.
- Affiliations
- Tokyo Institute of Technology (JP)
- Kyoto University (JP)
- Corresponding author
- Ohsumi, Yoshinori
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2013-10-28
- Volume
- 203
- Issue
- 2
- Pages
- 299-313
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3812978
- OpenAlex
- W2151084479
- Cited by
- 119
- References
- 53
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 9 · 2020: 12 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 13 · 2015: 14 · 2014: 14 · 2013: 2
- FWCI
- 10.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (23570190, 24659017, 25460063)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- autophagy, Vps34, ATG14, VPS15, phosphatidylinositol 3-phosphate, autophagosome formation, protein complex formation, homodimerization, yeast
- MeSH terms
- Autophagy-Related Proteins, Autophagy, Genotype, Mutation, Phenotype, Saccharomyces cerevisiae, Signal Transduction, Gene Expression Regulation, Fungal, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Multiprotein Complexes, Immunoprecipitation, Protein Interaction Domains and Motifs, Protein Multimerization, Class III Phosphatidylinositol 3-Kinases, Vacuolar Sorting Protein VPS15
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