Lysosomes and Autophagy: A Crucial Role in Cellular Health and Disease

The contribution of lysosomes in autophagy has also been reported by multiple studies [22][23, 24][25]. Autophagosome numbers increase not only from lysosome-dependent activation of mTORC1, but may also be caused by inhibiting lysosome-mediated proteolysis or inhibiting autophagosome-lysosome fusion [1]. TFEB is a master regulator for transcription of genes involved in lysosomes biogenesis [26], affecting the TFEB pathway could block autophagy flux by targeting lysosomes [25][23, 24]. Meanwhile, the inhibition of lysosomes degradation by lysosomal inhibitors (bafilomycin A1 or chloroquine) could be used interchangeably to block autophagy in in vitro experiments to assess autophagy flux [1].

Apart from these molecules, other noncanonical autophagy-related proteins have been demonstrated in 'Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)', more details could be found in this Guideline [1]. These include proteins such as LC3-associated phagocytosis (LAP), which is a process where LC3 is recruited to phagosomes to facilitate their degradation; LC3B-II-dependent phagocytosis, which is a process where LC3B-II is recruited to the phagosome membrane to promote phagocytosis; and LC3-associated endocytosis (LANDO), which is a process where LC3 is involved in endocytosis and subsequent lysosomal degradation. These noncanonical autophagy-related proteins are important for the clearance of intracellular pathogens and for the maintenance of cellular homeostasis.

In summary, autophagy is a highly regulated process that involves a complex network of signaling pathways and protein interactions. The involvement of lysosomes in autophagy is crucial for the degradation of autophagosomes and the recycling of cellular components. Dysregulation of autophagy has been implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and infectious diseases. Therefore, understanding the molecular mechanisms involved in autophagy and lysosomal function is critical for the development of new therapeutic strategies for these diseases.