# LC3 lipidation

LC3 lipidation is a key step in building an autophagosome (the autophagy 'garbage bag'). It attaches the autophagy protein LC3 to a membrane fat (phosphatidylethanolamine, or PE), converting the free form (LC3-I) into the membrane-anchored form (LC3-II). The reaction runs through a ubiquitin-like cascade: an E1-like enzyme (ATG7), an E2-like enzyme (ATG3), and an E3-like complex (ATG5-ATG12-ATG16L1). It also needs an earlier signal (PI3P), made by the Beclin-1/VPS34 complex. The density of LC3-II on the membrane recruits selective-autophagy receptors (like p62 and NDP52). And it is the most widely used proxy for how many autophagosomes there are. In fact, the ratio of LC3-II to LC3-I (measured by immunoblot, with and without lysosome blockers) is a standard way to estimate your autophagic flux.

## Sources

- Kabeya Y, Mizushima N, Ueno T, et al.. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO Journal. https://doi.org/10.1093/emboj/19.21.5720
- Ishihara N, Hamasaki M, Yokota S, et al.. (2001). Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.12.11.3690

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_Canonical: https://longevity-switzerland.com/en/glossary/lc3-lipidation · Part of Longevity Cities · Updated 2026-06-22_