LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Open accessAbstract
Little is known about the protein constituents of autophagosome membranes in mammalian cells. Here we demonstrate that the rat microtubule-associated protein 1 light chain 3 (LC3), a homologue of Apg8p essential for autophagy in yeast, is associated to the autophagosome membranes after processing. Two forms of LC3, called LC3-I and -II, were produced post-translationally in various cells. LC3-I is cytosolic, whereas LC3-II is membrane bound. The autophagic vacuole fraction prepared from starved rat liver was enriched with LC3-II. Immunoelectron microscopy on LC3 revealed specific labelling of autophagosome membranes in addition to the cytoplasmic labelling. LC3-II was present both inside and outside of autophagosomes. Mutational analyses suggest that LC3-I is formed by the removal of the C-terminal 22 amino acids from newly synthesized LC3, followed by the conversion of a fraction of LC3-I into LC3-II. The amount of LC3-II is correlated with the extent of autophagosome formation. LC3-II is the first mammalian protein identified that specifically associates with autophagosome membranes.
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LC3II is a lipidated form of LC3.
“As LC3II is a lipidated form of LC3 (Kabeya et al., 2000), these results indicated an increase in autophagosome formation.”
From Inducible Rpt3, a Proteasome Component, Knockout in Adult Skeletal Muscle Results in Muscle Atrophy (2020) · cites this paper as Kabeya et al., 2000
The section on LC3 processing identifies LC3-II as a processed form of LC3, and the distribution results show that it associates with membranes. But the Discussion says the nature of the modification forming LC3-II “remains cryptic”; this paper does not establish that LC3-II is lipidated. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCytosolic LC3-I is conjugated to phosphatidylethanolamine (PE), and in this form LC3-II is recruited to the growing autophagosome membrane.
“The cytosolic form of LC3 (designated LC3-I) is conjugated to phosphatidylethanolamine (PE) and in this form (designated LC3-II) it is recruited to the growing autophagosome membrane [26].”
From LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy (2012) · cites this paper as [26]
The sections on LC3 processing and autophagosome-membrane localization report conversion of cytosolic LC3-I to LC3-II and association of LC3-II with autophagosome membranes (page numbers unavailable). Our copy does not identify phosphatidylethanolamine as the conjugated molecule or establish recruitment specifically to a growing membrane. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe Venus variant of YFP is brighter than mRFP and less sensitive to pH than GFP.
“Another alternative to mRFP or mCherry is to use the Venus variant of YFP, which is brighter than mRFP and less sensitive to pH than GFP.186”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [186]
The DNA constructions and LC3-II localization sections describe a GFP–LC3 construct and its use in microscopy. Searches for Venus/YFP, mRFP, brightness, and pH sensitivity found no passage comparing these fluorescent proteins, so our copy does not address the attributed claim. The indexed passages provide no page numbers. (LLM, conf=0.78)
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- Authors
- Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T.
- Affiliations
- National Institute for Basic Biology (JP)
- Juntendo University (JP)
- Kansai Medical University (JP)
- Corresponding author
- Yoshimori, Tamotsu
- ORCID
- Mizushima, Noboru
- Venue
- The EMBO Journal
- Published
- 2000-11-01
- Volume
- 19
- Issue
- 21
- Pages
- 5720-5728
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC305793
- OpenAlex
- W1977767269
- Cited by
- 6,605
- References
- 31
- Citations by year
- 2026: 135 · 2025: 173 · 2024: 226 · 2023: 272 · 2022: 287 · 2021: 342 · 2020: 344 · 2019: 380 · 2018: 377 · 2017: 387 · 2016: 381 · 2015: 426 · 2014: 389 · 2013: 447 · 2012: 386
- FWCI
- 18.08
- Type
- journal article
- Language
- en
- Update notices
- erratum (2003-09-01)
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- National Institute for Basic Biology
- 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 › Ubiquitin and proteasome pathways
- Keywords
- LC3, autophagy, LC3-II, post-translational processing, C-terminal truncation, autophagosomes, yeast homologue
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Fungal Proteins, HeLa Cells, Humans, Intracellular Membranes, Microtubule-Associated Proteins, Molecular Sequence Data, Phagosomes, Protein Processing, Post-Translational, Subcellular Fractions, Transfection, Microscopy, Immunoelectron, Sequence Homology, Amino Acid, DNA Primers, Rats
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