Microtubule-associated protein 1 light chain 3 alpha (LC3A) (LC3A)

Microtubule-associated protein 1 light chain 3 alpha (LC3A) is a key member of the MAP1LC3 family and a mammalian homolog of the yeast Atg8 protein, serving as a central mediator in the autophagy pathway [5, 6]. It functions as a ubiquitin-like modifier that is essential for the formation, elongation, and maturation of autophagosomes, which are double-membrane vesicles that sequester damaged organelles and proteins for lysosomal degradation [7, 14]. LC3A exists in a cytosolic form (LC3A-I) that is lipidated to a membrane-bound form (LC3A-II) upon autophagy induction, making it a widely used biomarker for autophagic flux [11, 20]. In clinical contexts, LC3A is frequently overexpressed in various cancers, such as ovarian clear cell carcinoma and lung cancer, where it is associated with poor prognosis and resistance to chemotherapy [1, 13]. Therapeutic strategies targeting LC3A involve the use of autophagy inhibitors like hydroxychloroquine or novel covalent modulators like DC-LC3in-D5 to sensitize tumor cells to treatment [1, 16]. Beyond oncology, LC3A is implicated in neurodegenerative diseases and infections, where its role in cellular homeostasis and cargo clearance is critical for disease progression [2, 9, 16].

Other names

MAP1LC3AATG8EAutophagy-related protein LC3 AAutophagy-related ubiquitin-like modifier LC3 AMAP1 light chain 3-like protein 1Microtubule-associated proteins 1A/1B light chain 3A

Inhibition of autophagosome formation through covalent modification of the LC3 protein or lysosomal neutralization, leading to chemosensitization in cancer cells [1, 16].