Specific examples and circuitry of how atg8ylation controls different signaling and stress response processes at the lysosome. Note that both mTOR and AMPK as well as their regulatory elements are localized at the lysosome. AMPK positively regulates canonical autophagy, whereas mTOR negatively regulates this atg8ylation-associated process. Boxes 1–4 describe four of the expanding list of autophagy-independent atg8ylation-dependent processes. This includes control of AMPK, mTOR, and TFEB by mATG8s and atg8ylation (Boxes 1–3). Box 4–associated schematic depicts how increase in lumenal pH (phagosomes, organelles of the endolysosomal network) by the action of the influenza viroporin M2 that acts as an H⁺ channel or proton scavenging during superoxide production induce membrane atg8ylation (LC3 shown as an example of LAP and LAP-related processes). This occurs due to the increased recruitment of ATG16L1 via its direct binding to the V1 subunit of vacuolar H⁺-ATPase, upon elevated V₁V₀ assembly on membranes in response to neutralization of the lumenal pH. Further details in the text.