5.6. Caution merited to avoid excessive mitophagy induction
As mentioned above, mild mitophagy induction is a benign process in mammalian cells, whereas excessive mitophagy may have adverse effects. In line with this, caution should be exercised when implementing combinational therapeutic systems. Currently, there is no available method to restrain mitophagy overactivation upon using mitophagy inducers. Thus, melatonin therapy and accessory therapeutic agents might lead to mitophagy overactivation. However, executing pre-clinical studies may show us a safe regimen for applying these agents. Thus, we propose dose-finding and duration-finding studies to identify optimal drug concentrations and treatment durations to avoid excessive mitophagy activation, while maintaining mild induction. Of note, some drugs also exhibit different effects in terms of intensity at different times of the day, which is referred to as chronopharmacology.