Lysosome-associated membrane proteins (LAMPs) regulate intracellular positioning of mitochondria in MC3T3-E1 cells

• Published in: Experimental cell research Vol. 331; no. 1; pp. 211 - 222
• Main Authors: Rajapakshe, Anupama R., Podyma-Inoue, Katarzyna A., Terasawa, Kazue, Hasegawa, Katsuya, Namba, Toshimitsu, Kumei, Yasuhiro, Yanagishita, Masaki, Hara-Yokoyama, Miki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015; Elsevier BV
• Subjects: Animals; Blotting, Western; Cell growth; Cells, Cultured; Cellular biology; Cytoplasm - metabolism; Glycosylation; Immunoenzyme Techniques; Intracellular Membranes - metabolism; Intracellular positioning; Lysosomal Membrane Proteins - antagonists & inhibitors; Lysosomal Membrane Proteins - genetics; Lysosomal Membrane Proteins - metabolism; Lysosomal-Associated Membrane Protein 2 - antagonists & inhibitors; Lysosomal-Associated Membrane Protein 2 - genetics; Lysosomal-Associated Membrane Protein 2 - metabolism; Lysosome-associated membrane proteins (LAMPs); Lysosomes; Lysosomes - metabolism; Mice; Mitochondria; Mitochondria - metabolism; Osteoblasts - cytology; Osteoblasts - metabolism; Proteins; RNA, Small Interfering - genetics; Intracellular positioning; Lysosomes; Mitochondria; Lysosome-associated membrane proteins (LAMPs)
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2014.09.014

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. •LAMPs downregulation enhanced perinuclear mitochondrial localization in cells.•The perinuclear localization was stronger with the LAMP-1 deficiency.•Lysosomes and mitochondria were more perinuclear in osteocytic cells.•LAMPs downregulation did not affect mitochondrial localization in osteocytic cells.