Fig. (4).

Effects of mitochondrial Ca²⁺ on autophagy. A. Mitochondrial Ca²⁺ inhibits autophagy: A moderate transfer of Ca²⁺ from the ER to mitochondria through IP₃R, triggers ATP production that subsequently inactivates AMPK-dependent autophagy. B. Under stress, mitochondrial Ca²⁺ can activate autophagy: Mitochondria overloaded with Ca²⁺ are permeabilized and damaged. This promotes mitophagy and also activates calcineurin, which enhances NF-KappaB-mediated transcription of Beclin 1. Also, NIX buried in the outer mitochondrial membrane induces Ca²⁺ transfer from the ER to mitochondria and activates mitophagy. See text for further details.