title: StarD7 mediates the intracellular trafficking of phosphatidylcholine to mitochondria.
abstract: Steroidogenic acute regulatory protein-related lipid transfer (START) domains, found in 15 mammalian proteins termed StarD1-StarD15, are lipid-binding domains implicated in the intracellular lipid transport systems. In the present study, we analyzed the lipid ligand and function of StarD7. We found two variable forms of mammalian StarD7, termed StarD7-I and StarD7-II. Unlike StarD7-II, StarD7-I contained a mitochondrial-targeting sequence in its N terminus. Overexpressed StarD7-I tagged with V5/His in HEPA-1 cells was mainly observed in the mitochondria of cells prepared at low cellular density, but it was distributed in the cytoplasm of high density cells. StarD7-II was constantly distributed in the cytoplasm at any cellular density. Endogenous StarD7 in HEPA-1 cells and rat liver was also distributed in both the cytoplasm and the mitochondria. A protease K protection assay indicated that the mitochondrial StarD7 was associated with the outer mitochondrial membrane. The purified recombinant StarD7 specifically catalyzed the transfer of PC between lipid vesicles in vitro. Furthermore, the intracellular transport of fluorescent PC that was exogenously incorporated into the mitochondria was increased in cells that overexpressed StarD7-I. These results suggest that StarD7 facilitates the delivery of PC to mitochondria in non-vesicular system.
authors.affiliation: Department of Biochemistry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Horibata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010713:Phosphatidylcholines; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C483475:STARD7 protein, human