title: Lysosome-associated membrane proteins (LAMPs) regulate intracellular positioning of mitochondria in MC3T3-E1 cells.
abstract: The intracellular positioning of both lysosomes and mitochondria meets the requirements of degradation and energy supply, which are respectively the two major functions for cellular maintenance. The positioning of both lysosomes and mitochondria is apparently affected by the nutrient status of the cells. However, the mechanism coordinating the positioning of the organelles has not been sufficiently elucidated. Lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2) are highly glycosylated proteins that are abundant in lysosomal membranes. In the present study, we demonstrated that the siRNA-mediated downregulation of LAMP-1, LAMP-2 or their combination enhanced the perinuclear localization of mitochondria, in the pre-osteoblastic cell line MC3T3-E1. On the other hand, in the osteocytic cell line MLO-Y4, in which both the lysosomes and mitochondria originally accumulate in the perinuclear region and mitochondria also fill dendrites, the effect of siRNA of LAMP-1 or LAMP-2 was barely observed. LAMPs are not directly associated with mitochondria, and there do not seem to be any accessory molecules commonly required to recruit the motor proteins to lysosomes and mitochondria. Our results suggest that LAMPs may regulate the positioning of lysosomes and mitochondria. A possible mechanism involving the indirect and context-dependent action of LAMPs is discussed.
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Anupama R
authors.initials: AR
authors.lastname: Rajapakshe
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Podyma-Inoue
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Terasawa
authors.affiliation: JAXA/Institute of Space and Astronautical Sciences, 3-1-1 Yoshino-dai, Chuo-ku, Sagamihara 252-5210, Kanagawa, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Namba
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kumei
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yanagishita
authors.affiliation: Section of Biochemistry, Department of Hard Tissue Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: m.yokoyama.bch@tmd.ac.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Hara-Yokoyama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006031:Glycosylation; D007124:Immunoenzyme Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D034741:RNA, Small Interfering; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1
keywords: Intracellular positioning; Lysosome-associated membrane proteins (LAMPs); Lysosomes; Mitochondria