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Mitophagy inhibits proliferation by decreasing cyclooxygenase-2 (COX-2) in arsenic trioxide-treated HepG2 cells
Zhidan Niu1, Wenya Zhang1, Xueyan Gu1
1Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Abstract:
Mitochondrial damage can trigger mitophagy and eventually suppress proliferation. However, the effect of mitophagy on proliferation remains unclear. In this study, HepG2 cells were used to assess mitophagy and proliferation arrest in response to As2O3 exposure. The stimulatory effect of As2O3 on mitophagy was investigated by assessing morphology (mitophagosome and mitolysosome) and relevant proteins (PINK1, LC3 II/I, and COX IV). Additionally, the relationship of mitophagy and proliferation was explored through the use of mitophagy inhibitors (CsA, Mdivi-1). Interestingly, the inhibition of mitophagy rescued proliferation arrest by restoring COX-2 protein level and countered the elimination of mitochondria-located COX-2 and up-regulated the COX-2 mRNA level. Taken together, our findings indicated that mitophagy can be induced and can inhibit proliferation by reducing COX-2 in HepG2 cells during As2O3 treatment.
Insights
Arsenic trioxide (As2O3) induces mitophagy, a process that suppresses cell proliferation by reducing COX-2 levels in HepG2 cells. Inhibiting mitophagy rescues proliferation arrest, highlighting mitophagy
Area of Science:
- Cell Biology
- Molecular Biology
- Toxicology
Background:
- Mitochondrial damage is known to initiate mitophagy, a cellular process that clears damaged mitochondria.
- While mitophagy is linked to proliferation suppression, its precise role in this context remains incompletely understood.
- Arsenic trioxide (As2O3) is a compound with known cellular effects, including potential impacts on mitochondrial function and cell proliferation.
Purpose of the Study:
- To investigate the effect of As2O3 exposure on mitophagy in HepG2 cells.
- To determine the relationship between mitophagy and proliferation arrest induced by As2O3.
- To elucidate the role of COX-2 in As2O3-induced mitophagy and proliferation suppression.
Main Methods:
- HepG2 cells were treated with As2O3 to induce mitophagy.
- Mitophagy was assessed by examining cellular morphology (mitophagosomes, mitolysosomes) and key proteins (PINK1, LC3 II/I, COX IV).
- Mitophagy inhibitors (Cyclosporine A, Mdivi-1) were used to explore the link between mitophagy and proliferation.
Main Results:
- As2O3 exposure stimulated mitophagy in HepG2 cells, evidenced by morphological changes and altered protein levels.
- Inhibition of mitophagy using CsA or Mdivi-1 rescued proliferation arrest.
- Mitophagy inhibition restored COX-2 protein levels and countered mitochondrial COX-2 elimination, alongside up-regulating COX-2 mRNA.
Conclusions:
- As2O3 induces mitophagy in HepG2 cells.
- Mitophagy contributes to proliferation inhibition during As2O3 treatment by reducing COX-2 levels.
- Targeting mitophagy may offer a strategy to counteract As2O3-induced proliferation arrest.
