Abstract Opioids are commonly used drugs in the clinic, mainly targeting different subtypes of opioid receptors distributed in central and peripheral neurons. They are the preferred drugs for treating acute pain or cancer pain. Delta opioid receptor(DOR) agonists are opioid drugs that target the delta opioid receptor. In recent years, they have received widespread attention due to their ability to improve ischemia/reperfusion injury in multiple organs such as the heart, brain, and liver, as well as their potential for treating mental and neurological disorders. This review summarizes the mechanism research of DOR agonists in treating a variety of diseases, prospects their clinical application prospects, and finds that DOR agonists may exert anti-ischemia/reperfusion injury effects on organs by reducing apoptosis and mitochondrial damage, and activating various signaling pathways; they also exhibit anti-inflammatory, antidepressant, and therapeutic effects on neurodegenerative diseases, providing a new perspective for the application of DOR agonists in treating related diseases.

OBJECTIVE Mitochondria plays a crucial role in cellular homeostasis by regulating various pro-cesses,including calcium signaling and mitophagy.This study aimed to explore the involvement of prohibitin 2(PHB2),an inner mitochondrial membrane protein,in the modulation of mitochondrial calcium dynamics and mitoph-agy.METHODS HEK293T cells were used as the experi-mental cells and were divided into control,PHB2 knock-down,and PHB2 overexpression groups.To evaluate mitochondrial calcium dynamics,Rhod-2 AM and Mito-Tracker Green fluorescence dyesrhod-2 staining and laser confocal microscopy were employed to visualize mito-chondrial calcium imaging.Additionally,Green-5N was utilized to measure the rate of mitochondrial calcium uptake.The mitochondrial membrane potential was assessed using JC-10 staining and laser confocal micros-copy,while cellular ATP levels were determined using ATP assay kits.Furthermore,mitochondrial autophagy was induced by treatment with CCCP,and the expression lev-els of TOM20,LC3,and PARKIN,key mitophagy-related proteins,were analyzed using Western blotting.RESULTS The results demonstrated that compared to the control group,the overexpression of PHB2 increased mitochon-drial calcium concentration,mitochondrial calcium uptake rate,ATP level and expression levels of LC3 and PAR-KIN,but decreased mitochondrial membrane potential and TOM20 expression.In contrast,PHB2 knockdown reduced mitochondrial calcium concentration,ATP level and expression levels of LC3 and PARKIN,but elevated mitochondrial membrane potential,and TOM20 expres-sion.CONCLUSION This study provides evidence that PHB2 plays a vital role in regulating mitochondrial calci-um dynamics,which in turn influences mitochondrial func-tion and modulates mitochondrial autophagy.These find-ings contribute to our understanding of the molecular mechanisms underlying the interplay between PHB2,mitochondrial calcium signaling,and mitophagy.