Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells

Abstract

Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

“…The proinflammatory profile has been extensively associated with the metabolic shift to glycolysis and accumulation of dysfunctional mitochondria . These are characteristics observed in lipopolysaccharide (LPS)‐activated Mϕs, and also in polarized M1 Mϕs.…”

“…Earlier studies utilized a high dose of 200 µM of etomoxir, which disturbs intracellular coenzyme A (CoA) homeostasis and inhibits M2 polarization . Mϕs can present different metabolic profiles depending on where they are located and which roles they are supposed to engage . The patterns of metabolic behavior in resident Mϕs result in distinct immune profiles, which are important to attend specific tissue necessities.…”

Causal roles of mitochondrial dynamics in longevity and healthy aging

“…Fused mitochondrial networks allow efficient exchange of metabolites, transmission of membrane potential from mitochondria in one part of the cell to the other, increased ATP production, and decreased ROS production. Additionally, fusion reduces endoplasmic reticulum (ER)‐mitochondrial Ca 2+ transfer to prevent Ca 2+ induced cell death . Importantly, mitochondrial fusion helps mitigate mitochondrial stress by fusing the contents of partially damaged mitochondria with healthy mitochondria as a form of complementation.…”

Ameliorative role of aspirin in paraquat‐induced lung toxicity via mitochondrial mechanisms

“…Mitochondria also contribute to PQ‐induced ROS generation; hence, cell apoptosis in mouse alveolar type II cells . PQ accumulates in mitochondria and induces an increment in superoxide radical production .…”

“…In this study, concomitant with an increase in lung injury, pulmonary fibrosis, lung mitochondrial injuries occurred in the animals treated with PQ. Mitochondria can be determined as an important target to treat lung injury by PQ poisoning since mitochondria play an important role in the inflammatory response …”