Autophagy protein in lysosomal stress and physiology
Proton pump V-ATPase with its cytoplasmic V1 domain and the membrane-embedded V0 domain plays a crucial role in lysosomal acidification process.
The authors show that ATG16L1’s ability to efficiently bind V-ATPase was required for its inhibitory role in endolysosomal acidification and for control of Mycobacterium tuberculosis infection in mice.
Meachanistically ATG16L binds to V1H of the v-ATPase under normal conditions reducing the lysosomal acidification> Under stress or damage, ATG16L-dependent CASM activation occurs with increased v-ATPase assembly. Increased acidification may necessitate ATG16L disengagement.
https://rupress.org/jcb/article/224/10/e202509030/278321/ATG16L-strikes-again-New-findings-link-lysosome
