Mitoquinone mitigates paraquat‐induced A549 lung epithelial cell injury by promoting MFN1/MFN2‐mediated mitochondrial fusion

Abstract

Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria‐targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ‐induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ‐induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose‐dependent manner, while MitoQ remarkably mitigated the PQ‐induced cell viability suppression. Besides this, PQ‐mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ‐induced lung epithelial cell injury by promoting MFN1/MFN2‐mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ‐induced lung injury.

Biotoxicity of paraquat to lung cells mediated by endoplasmic reticulum-mitochondria interactionMitochondrial dysfunction exposure mediates paraquat biotoxicity to lung tissue cells: The role of endoplasmic reticulum stress

“…During PQ-induced free radical production, mitochondria are both the main site and the primary organelle for free radical damage [31,32]. Meanwhile, mitochondria are also central link organelles in the apoptotic pathway.…”

Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction

“…Studies have shown that ROS-mediated mitochondrial fission lead to PQ-induced neuronal cell injury ( Chen et al, 2021 ). Promoting MFN2-mediated mitochondrial fusion protects against PQ-induced lung epithelial cell injury ( Liu et al, 2022 ). Our findings confirmed that PQ downregulated the protein expression of long-chain OPA1 and MFN2, thereby inhibiting mitochondrial fusion.…”