2022-033 – Atg8ylation Coordinates Stress Granule Formation and mTOR Inactivation in Response to Lysosomal Damage


Mammalian ATG factors participate in several processes including canonical and noncanonical autophagy variations and have been implicated in numerous diseases and physiological conditions. Several modules containing subsets of ATGs are necessary for canonical autophagy, whereas their subsets but not all modules play roles in noncanonical functions. Several of these processes are under the control of metabolic regulators, mTOR and AMPK, with signals transduced to the ATG apparatus. In other cases, ATGs can play unique roles such as the mammalian Atg8 proteins, which can act even upstream of lysosomally positioned regulators such as mTOR or TFEB, as evident during starvation or lysosomal damage. Lysosomal damage induces stress granule (SG) formation as a part of homeostatic responses to stressors that require adjustments in cellular processes until lysosomal functionality is restored. Thus, there is a need for a method to adjust and understand the cellular processes seen with lysosomal damage so that homeostasis can be restored after stress.

Technology Description
Researchers at the University of New Mexico’s department of Molecular Genetics & Microbiology have reported that cells employ Atg8ylation to control and coordinate stress granule (SG) and mTOR responses to lysosomal damage. For instance, a subset of mammalian Atg8s perform a dual action in balancing SG formation and mTOR inactivation. This relationship provides proper tuning of the two systems participating in protein translation arrest with selective translation of stress-protective elements during integrated stress response (ISR).


  • Controls responses to lysosomal damage
  • Makes appropriate adjustments in protein translation during stress
  • Limits SG formation and inhibits translation by both sequestering mRNAs in SGs and inhibiting mTOR
  • Balances contributions leading to a state of homeostasis

Potential Applications

  • Cancer Therapeutics
  • Neurodegenerative Disease
  • Viral Infections
    • COVID-19

Contact Information

Name: Gregg Banninger

Email: GBanninger@innovations.unm.edu

Phone: 505-272-7908