Nucleophagy: from homeostasis to disease

Types of autophagy. Macroautophagy involves the formation of the autophagosome. Initiation occurs with Unc-51-like kinase 1 activation and concomitant triggering of the phosphatidyl-inositol-3-kinase complex, Vps15/Vps34/Beclin 1 complex. In turn, two ubiquitin conjugation systems, ATG5/ATG7/ATG12 and LC3, are required for autophagosome formation and maturation. Autophagosome–lysosome fusion allows for degradation of autophagic substrates, such as p62. Microautophagy happens with direct interaction of the substrate and the lysosome. Chaperone-mediated autophagy requires chaperone targeting of specific proteins with the pentapeptide motif KFERQ to the lysosome-associated membrane protein LAMP-2