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Exp Cell Res. 2015 Feb 1;331(1):211-22. doi: 10.1016/j.yexcr.2014.09.014. Epub 2014 Sep 22.

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

Author information

1
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.
2
JAXA/Institute of Space and Astronautical Sciences, 3-1-1 Yoshino-dai, Chuo-ku, Sagamihara 252-5210, Kanagawa, Japan.
3
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.

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.

KEYWORDS:

Intracellular positioning; Lysosome-associated membrane proteins (LAMPs); Lysosomes; Mitochondria

PMID:
25246127
DOI:
10.1016/j.yexcr.2014.09.014
[Indexed for MEDLINE]

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