What is the primary function of amphisomes?
Interplay macroautophagy and endocytic system produces hybrid intermediate called amphisome fusion product before lysosomal degradation. Autophagosome double-membrane vesicle size up to 1 micron bearing lipidated LC3-II cargo sequestered including mitochondria protein aggregates bacteria forms upon closure isolation membrane phagophore. Separately endocytic pathway internalizes surface receptors extracellular material into early endosomes marked Rab5 PI3P then matures Rab7 positive late endosomes multivesicular bodies MVBs intraluminal vesicles tetraspanins CD63 LAMP1 LBPA. Amphisome formation occurs when double-membrane autophagosome fuses late endosome driven SNARE syntaxin7 syntaxin8 Vti1b VAMP8 tethering HOPS complex Rab11 effectors ATG14 merging contents creating single hybrid organelle still bounded partially original outer autophagosome membrane plus endosomal membrane containing both LC3-II endosomal markers Rab7 Rab5 CD63. Structure subsequently fuses lysosome autolysosome where hydrolases cathepsins degrade autophagic endocytic cargo efficiently increasing capacity allowing delivery plasma membrane cargo autophagic compartments. ER-Golgi transport via COPII COPI dynamin scission iron transport transferrin recycle distinct trafficking circuits unrelated amphisome formation and degradative merging quality control.
Ref: Nakamura & Yoshimori, Autophagy 2017: Amphisome formation from autophagosome-endosome fusion.