PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated...

Area of Science:

• Space Medicine
• Cell Biology
• Cardiovascular Physiology

Background:

• Long-term spaceflight causes cardiovascular dysfunction, impacting astronauts' physical health.
• The vascular endothelium is crucial for vascular function and sensitive to mechanical forces.
• Previous studies linked simulated microgravity to PINK1-dependent mitophagy in endothelial cells.

Purpose of the Study:

• To elucidate the mechanism of mitophagy induction in human umbilical vein endothelial cells (HUVECs) under simulated microgravity.
• To investigate the role of mitophagy in endothelial cell functional changes during simulated microgravity.
• To explore the interplay between mitophagy and the NLRP3 inflammasome pathway.

Main Methods:

• Simulated microgravity using a clinostat.
• Investigated ER stress, calcium transfer, and mitochondrial dynamics.
• Utilized mdivi-1 treatment and PINK1 knockdown to inhibit mitophagy.
• Assessed NLRP3 inflammasome activation, IL-1β release, endothelial hyperpermeability, and cell migration.

Main Results:

• Simulated microgravity induced ER stress, promoting calcium overload in mitochondria, leading to fission and mitophagy.
• Inhibition of mitophagy enhanced NLRP3 inflammasome activation.
• NLRP3 inflammasome activation increased endothelial hyperpermeability and cellular migration via IL-1β release.
• Mitophagy suppressed endothelial hyperpermeability and cell migration under simulated microgravity.

Conclusions:

• Clarified the mechanism of mitophagy induction by simulated microgravity in vitro.
• Demonstrated that mitophagy plays a protective role by inhibiting endothelial hyperpermeability and migration.
• Provided insights into vascular endothelial functional changes under microgravity conditions.