FIGURE 6.

CB2R pro-autophagy effect. Lysosomal CB2R activation results in release of intra-lysosomal Ca²⁺ through MCOLN1 (Mucolipin TRP Cation Channel 1). The released Ca²⁺ tethers mitochondria to lysosomes and some Ca²⁺ ions are transferred to the mitochondria where less ROS is then produced. Calcineurin (CaN) is also activated that then dephosphorylates TFEB causing its translocation to nucleus, downstream of which autophagosomes and lysosomes are generated. Green arrows represent CB2R stimulation of MCOLN1 to release Ca²⁺ ions that enter mitochondria and activate calcineurin (CaN) for TFEB nuclear translocation. V-ATPase, vacuolar-type ATPase; Ca-ATPase, Calcium ATPase; AAA-ATPase, ATPases Associated with diverse cellular activities.