title: PTPIP51 regulates mouse cardiac ischemia/reperfusion through mediating the mitochondria-SR junction.
abstract: Protein tyrosine phosphatase interacting protein 51 (PTPIP51) participates in multiple cellular processes, and dysfunction of PTPIP51 is implicated in diseases such as cancer and neurodegenerative disorders. However, there is no functional evidence showing the physiological or pathological roles of PTPIP51 in the heart. We have therefore investigated the role and mechanisms of PTPIP51 in regulating cardiac function. We found that PTPIP51 was markedly upregulated in ischemia/reperfusion heart. Upregulation of PTPIP51 by adenovirus-mediated overexpression markedly increased the contact of mitochondria-sarcoplasmic reticulum (SR), elevated mitochondrial Ca2+uptake from SR release through mitochondrial Ca2+uniporter. Inhibition or knockdown of mitochondrial Ca2+uniporter reversed PTPIP51-mediated increase of mitochondrial Ca2+and protected cardiomyocytes against PTPIP51-mediated apoptosis. More importantly, cardiac specific knockdown of PTPIP51 largely reduced myocardium infarction size and heart injury after ischemia/reperfusion. Our study defines a novel and essential function of PTPIP51 in the cardiac ischemia/reperfusion process by mediating mitochondria-SR contact. Downregulation of PTPIP51 improves heart function after ischemia/reperfusion injury, suggesting PTPIP51 as a therapeutic target for ischemic heart diseases.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Jia
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Yangpo
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for Human Disease Genomics, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D003324:Coronary Artery Disease / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015424:Reperfusion / Q000379:methods; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; C534801:PTPIP51 protein, mouse; D017027:Protein Tyrosine Phosphatases; D002118:Calcium