MAP1LC3B2 is essential for later stages of autophagosome maturation, distinct from LC3A/B, which primarily drives phagophore elongation . It interacts with GABARAP/GATE-16 subfamily proteins to facilitate membrane fusion .
Binds C-18 ceramides and anchors autophagolysosomes to damaged mitochondria during stress .
Maintains mitochondrial quality by eliminating excess organelles to prevent ROS accumulation .
Acts as a receptor for cargo recognition via LIR-containing proteins (e.g., p62) .
In autophagy-deficient cells, LC3-I accumulates in p62-positive aggregates, highlighting its role in cargo sequestration .
In cells lacking ATG9 or ATG16L1, endogenous LC3-I forms large puncta co-localizing with ubiquitinated p62 aggregates. This suggests:
Compartmentalization: LC3-I sequestration to p62-rich structures in autophagy impairment .
Functional Compensation: P62 acts as a platform for LC3-I aggregation, independent of LC3-II formation .
Mutations in MAP1LC3B2 and ATG4A were linked to recurrent HSV2 meningitis. Patient fibroblasts showed:
Impaired Autophagy Induction: Defective LC3-II formation post-HSV2 infection .
Viral Replication: Increased HSV2 replication due to autophagy failure .
Under hypoxia, tumor cells upregulate MAP1LC3B2 to sustain autophagy, enabling survival via:
Autophagic Flux: Replenishes LC3-II levels to counterbalance lysosomal degradation .
Therapeutic Vulnerability: Autophagy inhibition sensitizes hypoxic tumor cells to radiation .
The MAP1LC3B2 gene is located on chromosome 16 in humans . The protein encoded by this gene is a subunit of the larger MAP1A and MAP1B proteins, which are involved in microtubule assembly and are important for neurogenesis . LC3B2 is a ubiquitin-like modifier involved in the formation of autophagosomal vacuoles (autophagosomes), playing a significant role in the autophagy pathway .
LC3B2 is central to the autophagy pathway, where it functions in autophagy substrate selection and autophagosome biogenesis . Autophagy is a cellular process that involves the bulk degradation of cytoplasmic components, including damaged organelles and misfolded proteins, to maintain cellular homeostasis . LC3B2 is the most widely used marker of autophagosomes, the double-membrane vesicles that sequester cytoplasmic material for degradation .
Mutations or dysregulation of the MAP1LC3B2 gene have been associated with various diseases, including adenocarcinoma and adrenal gland ganglioneuroblastoma . The protein’s role in autophagy also implicates it in neurodegenerative diseases, where impaired autophagy can lead to the accumulation of toxic protein aggregates .