LC3B/p62-mediated mitophagy protects A549 cells from resveratrol-induced apoptosis

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.