2. Academic Validation
  3. Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival

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

  • Commun Biol. 2022 Jun 22;5(1):616. doi: 10.1038/s42003-022-03556-w.
Zhengtai Chen  # 1 2,  Hongqiang Wu  # 1 2,  Jianxin Yang 1 2,  Baolong Li 1 2,  Jian Ding 1 2,  Sheng Cheng 1 2,  Nageeb Bsoul 1 3,  Chenxi Zhang 4,  Jiaorong Li 3,  Haixiao Liu 5 6,  Damu Lin 7,  Weiyang Gao 8 9
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, 325000, Zhejiang Province, China.
  • 3 Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Orthopedics, The Number 6 Hospital of Ningbo, Ningbo, China.
  • 5 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. spineliu@163.com.
  • 6 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, 325000, Zhejiang Province, China. spineliu@163.com.
  • 7 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. ensita@163.com.
  • 8 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. weiyanggaoi@126.com.
  • 9 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, 325000, Zhejiang Province, China. weiyanggaoi@126.com.
  • # Contributed equally.
PMID: 35732814 DOI: 10.1038/s42003-022-03556-w
Abstract

The random-pattern skin FLAP is a crucial technique in reconstructive surgery and FLAP necrosis caused by ischemia/reperfusion injury is a major postoperative complication. Herein, we investigated the mechanism of Mitophagy induced by Melatonin (ML) and its effect on the survival of skin flaps. Our results demonstrated that ML could activate Mitophagy, ameliorate oxidative stress and alleviate Apoptosis in Tert-Butyl hydroperoxide solution (TBHP)-stimulated human umbilical vein endothelial cells in vitro. Inhibiting ML-induced Mitophagy considerably abolished its protective effects. Moreover, knockdown of Parkin by siRNA inhibited ML-induced Mitophagy, and subsequently exacerbated oxidative stress and Apoptosis. Further study demonstrated that inhibition of AMPK reversed these protective effects of ML and downregulated the expression of TFEB. In the vivo study, ML effectively promoted FLAP survival by activating Mitophagy and subsequently ameliorating oxidative stress and mitigating Apoptosis. These results established that ML is a potent agent capable for increasing random-pattern skin FLAP survival by activating Parkin-dependent Mitophagy through the AMPK-TFEB signaling pathway.

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