Baicalein Activates Parkin-Dependent Mitophagy through NDP52 and OPTN

Area of Science:

• Cellular Biology
• Biochemistry
• Hepatology

Background:

• Autophagy maintains cellular homeostasis and organelle quality control.
• Mitophagy, a selective form of autophagy, regulates mitochondrial turnover and is implicated in liver disease pathogenesis.
• The molecular mechanisms of hepatic mitophagy and potential modulators remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms of mitophagy regulation in liver cells.
• To identify small molecules that can modulate hepatic mitophagy.
• To investigate the role of baicalein in inducing mitophagy in liver cells.

Main Methods:

• Human hepatoma cells were treated with baicalein.
• Autophagy and mitophagy induction were assessed.
• Mitochondrial Parkin and TBK1 translocation was analyzed.
• Phosphorylation of TBK1 and ubiquitin was examined.
• Autophagy cargo receptors NDP52 and OPTN were identified.

Main Results:

• Baicalein induces complete autophagy, including autolysosome maturation, in human hepatoma cells.
• Baicalein-induced autophagy specifically targets mitochondria for degradation (mitophagy).
• Baicalein promotes the translocation of Parkin and TBK1 to mitochondria, initiating mitophagy.
• Phosphorylation of TBK1 (Ser172) and ubiquitin (Ser65) are key events in baicalein-induced mitophagy.
• NDP52 and OPTN act as crucial cargo receptors in baicalein-activated mitophagy.

Conclusions:

• This study delineates the molecular process of Parkin-dependent mitophagy in liver cells.
• Baicalein is identified as a novel and effective inducer of hepatic mitophagy.
• These findings provide insights into potential therapeutic strategies for liver diseases involving mitophagy dysfunction.