Lycopene mitigates DEHP-induced hepatic mitochondrial quality control disorder via regulating SIRT1/PINK1/mitophagy axis and mitochondrial unfolded protein response.

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is a hazardous chemical which is used as a plasticizer in the plastic products. Lycopene (LYC) is a carotenoid that has protective roles against cellular damage in different organs. The present study sought to explore the role of the interaction between mitophagy and mitochondrial unfolded protein response (UPRmt) in the LYC mitigating DEHP-induced hepatic mitochondrial quality control disorder. The mice were treated with LYC (5\u202fmg/kg) and/or DEHP (500 or 1000\u202fmg/kg). In our findings, LYC prevented DEHP-induced histopathological alterations including steatosis and fibrosis, and ultrastructural injuries including decreased mitochondrial membrane potential (ΔΨm) and mitochondria volume density. Furthermore, LYC alleviated DEHP-induced mitochondrial biogenesis disorder by suppressing SIRT1-PGC-1α axis, PINK1-mediated mitophagy and the activation of mitochondrial unfolded protein response (UPRmt). This research suggested that LYC could prevent DEHP-induced hepatic mitochondrial quality control disorder via regulating SIRT1/PINK1/mitophagy axis and UPRmt. The present study provided a current understanding about the potential implication of the SIRT1/PINK1/mitophagy axis and UPRmt in LYC preventing DEHP-induced hepatic mitochondrial quality control disorder.