LC3I

LC3I, or LC3-I, refers to the cytosolic, non-lipidated form of the autophagy-related protein LC3 (microtubule-associated protein 1A/1B-light chain 3). LC3 is part of the Atg8 family and plays a central role in autophagosome formation, maturation, and cargo recruitment. In its LC3-I form, the protein exists in the cytosol and serves as a precursor that becomes activated for membrane association.

Biochemically, LC3I is generated by cleavage of pro-LC3 by the protease ATG4, exposing a glycine at the C-terminus. This exposed glycine allows conjugation to phosphatidylethanolamine (PE) in a process driven by the ubiquitin-like enzymes ATG7 (E1) and ATG3 (E2), forming LC3-II. LC3-II is the lipidated, membrane-associated form that localizes to autophagosomes. The LC3-I to LC3-II conversion is widely used as a molecular marker of autophagy, and the relative abundance of LC3-I and LC3-II can reflect autophagic flux, especially when combined with other assays.

In research and diagnostics, LC3I and LC3II levels are commonly assessed by Western blotting or immunofluorescence to monitor autophagy under various conditions, such as nutrient deprivation, pharmacological modulation, or disease states. Changes in the LC3-I/LC3-II ratio, along with autophagosome number and turnover, inform studies in cancer, neurodegeneration, and metabolic disorders. While LC3-II is the membrane-bound form associated with autophagosomes, LC3I serves as the cytosolic precursor and a precursor indicator of autophagic activation.

See also: autophagy, LC3, autophagosome, ATG genes.