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Cited by 17Autophagy in Disease and TherapyFungal and yeast genetics researchCellular transport and secretion

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Atg15 is a vacuolar phospholipase that disintegrates organelle membranes

Open access
Watanabe, Yasunori, Iwasaki, Yurina, Sasaki, Kyoka, Motono, Chie, Imai, Kenichiro, Suzuki, Kuninori·2023·Cell Reports
DOI 10.1016/j.celrep.2023.113567

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Abstract

Atg15 (autophagy-related 15) is a vacuolar phospholipase essential for the degradation of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies, hereinafter referred to as intravacuolar/intralysosomal autophagic compartments (IACs), but it remains unknown if Atg15 directly disrupts IAC membranes. Here, we show that the recombinant Chaetomium thermophilum Atg15 lipase domain (CtAtg15(73–475)) possesses phospholipase activity. The activity of CtAtg15(73–475) was markedly elevated by limited digestion. We inserted the human rhinovirus 3C protease recognition sequence and found that cleavage between S159 and V160 was important to activate CtAtg15(73–475). Our molecular dynamics simulation suggested that the cleavage facilitated conformational change around the active center of CtAtg15, resulting in an exposed state. We confirmed that CtAtg15 could disintegrate S. cerevisiae IAC in vivo . Further, both mitochondria and IAC of S. cerevisiae were disintegrated by CtAtg15. This study suggests Atg15 plays a role in disrupting any organelle membranes delivered to vacuoles by autophagy.

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Research works printed but not linked: 1

  1. Suzuki, 2002, Studies of cargo delivery to the vacuole mediated by autophagosomes in Saccharomyces cerevisiae, Dev. Cell, 3, 815, 10.1016/S1534-5807(02)00359-3 · DOI

Metadata

Authors
Watanabe, Y., Iwasaki, Y., Sasaki, K., Motono, C., Imai, K., & Suzuki, K.
Affiliations
  • Yamagata University (JP)
  • The University of Tokyo (JP)
  • Waseda University (JP)
  • Global Research and Development Center for Business by Quantum-AI technology (JP)
  • Collaborative Research Institute for Innovative Microbiology, The University of Tokyo (JP)
Corresponding author
  • Watanabe, Yasunori
  • Suzuki, Kuninori
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2023-12
Volume
42
Issue
12
Pages
113567
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2023.113567
OpenAlex
W4389955954
Cited by
17
References
50
Citations by year
2026: 9 · 2025: 5 · 2024: 3
FWCI
3.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
Funders
  • Japan Society for the Promotion of Science (20H05313, 21H03551, 21K19205, 22H02569, 22K06096, 23K11313)
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Science and Technology Agency (JP201032912)
  • Core Research for Evolutional Science and Technology
  • Japan Agency for Medical Research and Development (23ama121029j0002)
  • Naito Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
autophagy, Chaetomium thermophilum, proteolytic activation, conformational change, mitochondrial degradation, Saccharomyces cerevisiae
MeSH terms
Protein Domains, Autophagy, Chaetomium, Enzyme Activation, Fungal Proteins, Humans, Intracellular Membranes, Lipase, Mitochondria, Models, Molecular, Phospholipases, Recombinant Proteins, Saccharomyces cerevisiae, Vacuoles, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins, Molecular Dynamics Simulation

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.