PMID- 37245582
OWN - NLM
STAT- MEDLINE
DCOM- 20230703
LR  - 20240119
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 429
IP  - 2
DP  - 2023 Aug 15
TI  - The ultrastructural function of MLN64 in the late endosome-mitochondria membrane 
      contact sites in placental cells.
PG  - 113668
LID - S0014-4827(23)00215-X [pii]
LID - 10.1016/j.yexcr.2023.113668 [doi]
AB  - The close apposition between two different organelles is critical in essential 
      processes such as ion homeostasis, signaling, and lipid transition. However, 
      information related to the structural features of membrane contact sites (MCSs) 
      is limited. This study used immuno-electron microscopy and immuno-electron 
      tomography (I-ET) to analyze the two- and three-dimensional structures of the 
      late endosome-mitochondria contact sites in placental cells. Filamentous 
      structures or tethers were identified that connected the late endosomes and 
      mitochondria. Lamp1 antibody-labeled I-ET revealed enrichment of tethers in the 
      MCSs. The cholesterol-binding endosomal protein metastatic lymph node 64 (MLN64) 
      encoded by STARD3 was required for the formation of this apposition. The distance 
      of the late endosome-mitochondria contact sites was <20 nm, shorter than that in 
      STARD3-knockdown cells (<150 nm). The perturbation of cholesterol egress from the 
      endosomes induced by U18666A treatment produced a longer distance in the contact 
      sites than that in knockdown cells. The late endosome-mitochondria tethers failed 
      to form correctly in STARD3-knockdown cells. Our results unravel the role of 
      MLN64 involved in MCSs between late endosomes and mitochondria in placental 
      cells.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Nara, Atsuki
AU  - Nara A
AD  - Department of Bioscience, Nagahama Institute of Bioscience and Technology, Shiga, 
      526-0829, Japan. Electronic address: a_nara@nagahama-i-bio.ac.jp.
FAU - Inoue, Akimi
AU  - Inoue A
AD  - Department of Bioscience, Nagahama Institute of Bioscience and Technology, Shiga, 
      526-0829, Japan.
FAU - Aoyama, Yoshitaka
AU  - Aoyama Y
AD  - EM Application Department, EM Business Unit, JEOL Ltd., Tokyo 196-8558, Japan.
FAU - Yazawa, Takashi
AU  - Yazawa T
AD  - Department of Biochemistry, Asahikawa Medical University, Hokkaido, 078-8510, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230526
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Female
MH  - Pregnancy
MH  - Humans
MH  - *Carrier Proteins/metabolism
MH  - *Membrane Proteins/genetics/metabolism
MH  - Placenta/metabolism
MH  - Mitochondria/metabolism
MH  - Endosomes/metabolism
MH  - Mitochondrial Membranes/metabolism
MH  - Cholesterol/metabolism
OTO - NOTNLM
OT  - Electron microscopy
OT  - Endosomes
OT  - MLN64
OT  - Membrane contact site
OT  - Organelle structure
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/29 00:42
MHDA- 2023/07/03 06:41
CRDT- 2023/05/28 19:23
PHST- 2023/04/24 00:00 [received]
PHST- 2023/05/24 00:00 [revised]
PHST- 2023/05/25 00:00 [accepted]
PHST- 2023/07/03 06:41 [medline]
PHST- 2023/05/29 00:42 [pubmed]
PHST- 2023/05/28 19:23 [entrez]
AID - S0014-4827(23)00215-X [pii]
AID - 10.1016/j.yexcr.2023.113668 [doi]
PST - ppublish
SO  - Exp Cell Res. 2023 Aug 15;429(2):113668. doi: 10.1016/j.yexcr.2023.113668. Epub 
      2023 May 26.