title: PINK1-Parkin-Mediated Mitophagy Protects Mitochondrial Integrity and Prevents Metabolic Stress-Induced Endothelial Injury.
abstract: Mitochondrial injury and dysfunction, a significant feature in metabolic syndrome, triggers endothelial cell dysfunction and cell death. Increasing evidence suggests that mitophagy, a process of autophagic turnover of damaged mitochondria, maintains mitochondrial integrity. PINK1 (phosphatase and tensin homolog (PTEN)-induced putative kinase 1) and Parkin signaling is a key pathway in mitophagy control. In this study, we examined whether this pathway could protect mitochondria under metabolic stress. We found that palmitic acid (PA) induced significant mitophagy and activated PINK1 and Parkin in endothelial cells. Knocking down PINK1 or Parkin reduced mitophagy, leading to impaired clearance of damaged mitochondria and intracellular accumulation of mitochondrial fragments. Furthermore, PINK1 and Parkin prevented PA-induced mitochondrial dysfunction, ROS production and apoptosis. Finally, we show that PINK1 and Parkin were up-regulated in vascular wall of obese mice and diabetic mice. Our study demonstrates that PINK1-Parkin pathway is activated in response to metabolic stress. Through induction of mitophagy, this pathway protects mitochondrial integrity and prevents metabolic stress-induced endothelial injury.
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Liangshuai
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China; Department of Cell Biology and Anatomy, South Carolina University, Columbus, South Carolina29209, United States of America.
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
authors.affiliation: Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, P.R. China; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States of America; Texas Heart Institute, Houston, TX, United States of America.
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States of America; Texas Heart Institute, Houston, TX, United States of America.
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
mesh_terms: D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy; D009765:Obesity / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D065840:Protective Factors; D011494:Protein Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D015854:Up-Regulation; D000099202:PTEN-Induced Putative Kinase
chemical_list: D019308:Palmitic Acid; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein