Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps...

Area of Science:

• Biomedical Engineering
• Cell Biology
• Regenerative Medicine

Background:

• Flap necrosis is a significant complication in reconstructive surgery, often due to ischemia/reperfusion injury.
• Understanding the molecular mechanisms underlying flap survival is critical for improving surgical outcomes.

Purpose of the Study:

• To investigate the role of Melatonin (ML) in promoting skin flap survival.
• To elucidate the mechanism of ML-induced mitophagy and its impact on oxidative stress and apoptosis.

Main Methods:

• In vitro studies using Tert-Butyl hydroperoxide (TBHP)-stimulated human umbilical vein endothelial cells.
• In vivo studies assessing random-pattern skin flap survival in a preclinical model.
• Investigated the involvement of mitophagy, Parkin, AMPK, and TFEB signaling pathways.

Main Results:

• Melatonin (ML) activated mitophagy, reduced oxidative stress, and alleviated apoptosis in vitro.
• Inhibition of mitophagy or Parkin exacerbated oxidative stress and apoptosis.
• ML promoted in vivo skin flap survival by activating Parkin-dependent mitophagy via the AMPK-TFEB pathway.

Conclusions:

• Melatonin (ML) is a potent agent for enhancing random-pattern skin flap survival.
• ML-induced mitophagy, mediated by the AMPK-TFEB pathway, is a key mechanism for its protective effects.
• Targeting mitophagy presents a promising therapeutic strategy for preventing flap necrosis.