title: The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis.
abstract: Mitochondria synthesize select phospholipids but lack the machinery for synthesis of the most abundant mitochondrial phospholipid, phosphatidylcholine (PC). Although the phospholipid transfer protein Stard7 promotes uptake of PC by mitochondria, the importance of this pathway for mitochondrial and cellular homeostasis represents a significant knowledge gap. Haploinsufficiency for Stard7 is associated with significant exacerbation of allergic airway disease in mice, including an increase in epithelial barrier permeability. To test the hypothesis that Stard7 deficiency leads to altered barrier structure/function downstream of mitochondrial dysfunction, Stard7 expression was knocked down in a bronchiolar epithelial cell line (BEAS-2B) and specifically deleted in lung epithelial cells of mice (Stard7epi∆/∆). Stard7 deficiency was associated with altered mitochondrial size and membrane organization both in vitro and in vivo. Altered mitochondrial structure was accompanied by disruption of mitochondrial homeostasis, including decreased aerobic respiration, increased oxidant stress, and mitochondrial DNA damage that, in turn, was linked to altered barrier integrity and function. Both mitochondrial and barrier defects were largely corrected by targeting Stard7 to mitochondria or treating epithelial cells with a mitochondrial-targeted antioxidant. These studies suggest that Stard7-mediated transfer of PC is crucial for mitochondrial homeostasis and that mitochondrial dysfunction contributes to altered barrier permeability in Stard7-deficient mice.
authors.affiliation: Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Cheng-Lun
authors.initials: CL
authors.lastname: Na
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Luo
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wu
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Hogan
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Taosheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229-3039, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; C000600335:STARD7 protein, mouse