Related Experiment Video
Updated: Nov 18, 2025
Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes
Published on: May 19, 2023
LC3B/p62-mediated mitophagy protects A549 cells from resveratrol-induced apoptosis
Jiahua Zheng1, Shaochai Wei1, Tingting Xiao1
1Open Laboratory for Tumor Molecular Biology/Department of Biochemistry/The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Xinling Road 22, Shantou, China.
Aims:
Complicated mechanisms in cancer cells have been restricting the medicinal value of resveratrol (Res). The mechanisms by which Res exerts its anti-tumor activity in lung cancer cells have diverged among reports in recent years, whether cells choose to undergo autophagic cell death or apoptosis remains controversial. Yet, whether Res-induced autophagic cell death transforms into apoptosis is still unknown, and by which autophagy regulates programmed cell death is still undefined.
Main Methods:
Here, A549 cells were treated with Res to investigate the mechanisms of autophagy and apoptosis using western blot, immunofluorescence staining for LC3B.
Key Findings:
Non-canonical autophagy was induced by Res-treatment in a Beclin-1- and ATG5-independent manner, with apoptosis being activated simultaneously. Autophagy induced by Res was activated by rapamycin with decreased apoptosis, suggesting that autophagy may serve as a protective pathway in cells. Mitophagy was found to be induced by Res using fluorescence co-localization of mitochondria with lysosomes. Subsequently, it was identified that mitophagy was mediated by LC3B/p62 interaction and could be inhibited by LC3B knockout and p62 knockdown following increased apoptosis.
Significance:
In conclusion, the current results demonstrate that Res-induced non-canonical autophagy in A549 lung cancer cells with apoptosis activation simultaneously, while LC3B/p62-mediated mitophagy protects tumor cells against apoptosis, providing novel mechanisms about the critical role of mitophagy in regulating cell fate.
Insights
Resveratrol induces non-canonical autophagy and apoptosis in lung cancer cells. Mitophagy, mediated by LC3B/p62, protects these cells from apoptosis, revealing a novel regulatory mechanism in cell fate.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Mechanisms
Background:
- Resveratrol (Res) exhibits anti-tumor properties, but its precise mechanisms in lung cancer cells, particularly regarding cell death pathways, remain controversial.
- The interplay between Res-induced autophagy and apoptosis, and whether one can transform into the other, is not well-defined.
Purpose of the Study:
- To elucidate the mechanisms by which Resveratrol (Res) induces cell death in A549 lung cancer cells.
- To investigate the role of autophagy, specifically mitophagy, in regulating apoptosis in response to Res treatment.
Main Methods:
- A549 lung cancer cells were treated with Resveratrol.
- Western blot and immunofluorescence staining for LC3B were employed to analyze autophagy and apoptosis.
- LC3B knockout and p62 knockdown were performed to assess the role of specific proteins in mitophagy.
Main Results:
- Resveratrol induced non-canonical autophagy independently of Beclin-1 and ATG5, concurrently activating apoptosis.
- Autophagy induction by Resveratrol was associated with decreased apoptosis when activated by rapamycin, suggesting a protective role.
- Resveratrol-induced mitophagy, mediated by the LC3B/p62 interaction, was identified as a key pathway.
- Inhibition of mitophagy (via LC3B knockout or p62 knockdown) led to increased apoptosis.
Conclusions:
- Resveratrol triggers simultaneous non-canonical autophagy and apoptosis in A549 lung cancer cells.
- LC3B/p62-mediated mitophagy acts as a protective mechanism against Resveratrol-induced apoptosis in these cancer cells.
- This study reveals novel insights into the critical role of mitophagy in determining cancer cell fate.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...