Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer

Abstract StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitoc...

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Autores principales: Yasuhiro Horibata, Hiromi Ando, Motoyasu Satou, Hiroaki Shimizu, Satomi Mitsuhashi, Yasuo Shimizu, Masahiko Itoh, Hiroyuki Sugimoto
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:fac6ce5781f14fa1a440298d5e16ae902021-12-02T16:05:57ZIdentification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer10.1038/s41598-017-09205-12045-2322https://doaj.org/article/fac6ce5781f14fa1a440298d5e16ae902017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09205-1https://doaj.org/toc/2045-2322Abstract StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells. Re-expression of wild StarD7 can compensate these mitochondrial functions of StarD7-KO HEPA-1 cells. The precursor form of StarD7 is cleaved between Met76 and Ala77, and Ala77 and Ala78 in the TM domain to produce the mature form. These results suggest that StarD7 is anchored onto the OMM through its N-terminal TM domain, and the C-terminal START domain may extend into the cytoplasm and shuttle PC between the ER and OMM at the ER-mitochondria contact sites.Yasuhiro HoribataHiromi AndoMotoyasu SatouHiroaki ShimizuSatomi MitsuhashiYasuo ShimizuMasahiko ItohHiroyuki SugimotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yasuhiro Horibata
Hiromi Ando
Motoyasu Satou
Hiroaki Shimizu
Satomi Mitsuhashi
Yasuo Shimizu
Masahiko Itoh
Hiroyuki Sugimoto
Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
description Abstract StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells. Re-expression of wild StarD7 can compensate these mitochondrial functions of StarD7-KO HEPA-1 cells. The precursor form of StarD7 is cleaved between Met76 and Ala77, and Ala77 and Ala78 in the TM domain to produce the mature form. These results suggest that StarD7 is anchored onto the OMM through its N-terminal TM domain, and the C-terminal START domain may extend into the cytoplasm and shuttle PC between the ER and OMM at the ER-mitochondria contact sites.
format article
author Yasuhiro Horibata
Hiromi Ando
Motoyasu Satou
Hiroaki Shimizu
Satomi Mitsuhashi
Yasuo Shimizu
Masahiko Itoh
Hiroyuki Sugimoto
author_facet Yasuhiro Horibata
Hiromi Ando
Motoyasu Satou
Hiroaki Shimizu
Satomi Mitsuhashi
Yasuo Shimizu
Masahiko Itoh
Hiroyuki Sugimoto
author_sort Yasuhiro Horibata
title Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
title_short Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
title_full Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
title_fullStr Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
title_full_unstemmed Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
title_sort identification of the n-terminal transmembrane domain of stard7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/fac6ce5781f14fa1a440298d5e16ae90
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