autolysosomes

An autolysosome is a vesicular organelle formed during macroautophagy when an autophagosome fuses with a lysosome. This fusion creates a single compartment in which lysosomal hydrolases can degrade the contents of the autophagosome. The outer membrane of the autophagosome becomes part of the autolysosome membrane, while the inner membrane and the enclosed cargo are exposed to the lysosomal enzymes inside the acidic lumen.

Within the autolysosome, cargo such as damaged organelles, protein aggregates, and portions of cytoplasm are catabolized by lysosomal proteases, lipases, and other hydrolases, including cathepsins. The resulting breakdown products—amino acids, fatty acids, and simple sugars—are transported back to the cytosol for reuse, providing nutrients during periods of scarcity. Autophagic flux refers to the complete process from cargo sequestration to degradation and recycling.

Fusion between autophagosomes and lysosomes is mediated by specific proteins, including SNAREs such as STX17 on the autophagosome, SNAP29, and VAMP8 on the lysosome, as well as Rab GTPases and lysosomal membrane proteins like LAMP1/2. The process requires an acidic lysosomal environment and is tightly regulated by signaling pathways that respond to nutrient status, including mTORC1 inhibition and AMPK activation, which promote autophagy initiation, cargo selection receptors, and transcription factors such as TFEB that enhance lysosome biogenesis.

Dysfunction of autolysosome formation or activity is linked to diverse conditions, including neurodegenerative diseases and aging, where impaired degradation and defective nutrient recycling contribute to pathology.