mTORC-independent regulation of autophagy
Inositol 1,4,5-triphosphate (IP3) mediates mTORC-independent regulation of autophagy. IP3 binding to the endoplasmic reticulum (ER) instigates the release of calcium into the cytoplasm. Binding of agonists to L-type calcium channels also increases the cytoplasmic levels of calcium. The increase in cytoplasmic calcium induces the activation of a family of calcium-dependent cysteine proteases called calpains. Activated calpains cleave and activate Gsα, which induces adenylyl cyclase activity to increase the concentration of cAMP. Elevated cAMP activates the Epac molecule, which activates phospholipase C (PLC)-ε and increases IP3, thereby completing this regulatory loop.