Summary diagram depicting zinc and MT3 effects on autophagy and lysosomes. A. Under physiological conditions, normal signaling involving zinc release from MT3 contributes to the normal progression of autophagy, resulting in the degradation of abnormal protein aggregates and waste organelles. This pathway may be beneficial for cell survival. B. Under injurious oxidative stress conditions (e.g., H2O2 or HNE treatment), the events described in (A) are exaggerated. Hence, much more intense zinc release from MT3 is induced, and excess autophagy is activated. Excess autophagy and excess zinc accumulation in lysosomes ultimately leads to LMP and cell death. C. Downregulation of MT3 decreases zinc release from MT3, inhibiting lysosomal functions and reducing fusion between autophagosomes and lysosomes, resulting in a reduced autophagy flux. Under conditions of acute injury, this results in a reduction in both LMP and cell death, but it can be detrimental to cell survival under conditions of chronic stress by reducing autophagic degradation of abnormal proteins.