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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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) |
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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 |
work_keys_str_mv |
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