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Title:
Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis | Nature Communications
Description:
Accumulating evidence illustrates a fundamental role for mitochondria in lung alveolar type 2 epithelial cell (AEC2) dysfunction in the pathogenesis of idiopathic pulmonary fibrosis. However, the role of mitochondrial fusion in AEC2 function and lung fibrosis development remains unknown. Here we report that the absence of the mitochondrial fusion proteins mitofusin1 (MFN1) and mitofusin2 (MFN2) in murine AEC2 cells leads to morbidity and mortality associated with spontaneous lung fibrosis. We uncover a crucial role for MFN1 and MFN2 in the production of surfactant lipids with MFN1 and MFN2 regulating the synthesis of phospholipids and cholesterol in AEC2 cells. Loss of MFN1, MFN2 or inhibiting lipid synthesis via fatty acid synthase deficiency in AEC2 cells exacerbates bleomycin-induced lung fibrosis. We propose a tenet that mitochondrial fusion and lipid metabolism are tightly linked to regulate AEC2 cell injury and subsequent fibrotic remodeling in the lung. Mitochondria of alveolar type 2 epithelial cells (AEC2) in the lung have been suggested to play a role in the development of idiopathic pulmonary fibrosis (IPF). Here the authors show that loss of mitofusin1 and mitofusin2 in murine AEC2 cells leads to the development of lung fibrosis through the regulation of surfactant lipids.
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url:http://orcid.org/0000-0002-2813-4102
affiliation:
name:Weill Cornell Medicine
address:
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
type:PostalAddress
type:Organization
name:Mary E. Choi
affiliation:
name:Weill Cornell Medicine
address:
name:Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
type:PostalAddress
type:Organization
name:New York Presbyterian Hospital-Weill Cornell Medical Center
address:
name:New York Presbyterian Hospital-Weill Cornell Medical Center, New York, USA
type:PostalAddress
type:Organization
name:Chong-Jen Yu
affiliation:
name:Weill Cornell Medicine
address:
name:Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
type:PostalAddress
type:Organization
name:National Taiwan University
address:
name:Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
type:PostalAddress
type:Organization
name:Suzanne M. Cloonan
affiliation:
name:Weill Cornell Medicine
address:
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
type:PostalAddress
type:Organization
name:Augustine M. K. Choi
affiliation:
name:Weill Cornell Medicine
address:
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
type:PostalAddress
type:Organization
name:New York Presbyterian Hospital-Weill Cornell Medical Center
address:
name:New York Presbyterian Hospital-Weill Cornell Medical Center, New York, USA
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan
name:Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
name:Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:New York Presbyterian Hospital-Weill Cornell Medical Center, New York, USA
name:Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA
name:New York Presbyterian Hospital-Weill Cornell Medical Center, New York, USA
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