caa a22 4500 60623599X CHVBK 20210128101245.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2554-4 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2554-4 Impaired expression of the mitochondrial calcium uniporter suppresses mast cell degranulation [Elektronische Daten] [Tadahide Furuno, Narumi Shinkai, Yoshikazu Inoh, Mamoru Nakanishi] Calcium ion (Ca2+) uptake into the mitochondrial matrix influences ATP production, Ca2+ homeostasis, and apoptosis regulation. Ca2+ uptake across the ion-impermeable inner mitochondrial membrane is mediated by the mitochondrial Ca2+ uniporter (MCU) complex. The MCU complex forms a pore structure composed of several proteins. MCU is a Ca2+-selective channel in the inner-mitochondrial membrane that allows electrophoretic Ca2+ entry into the matrix. Mitochondrial Ca2+ uptake 1 (MICU1) functions as a Ca2+-sensing regulator of the MCU complex. Previously, by microscopic analysis at the single-cell level, we found that during mast cell activation, mitochondria capture cytosolic Ca2+ in two steps. Consequently, mitochondrial Ca2+ uptake likely plays a role in cellular function through cytosolic Ca2+ buffering. Here, we investigate the role of MCU and MICU1 in mitochondrial Ca2+ uptake and mast cell degranulation using MCU- and MICU1-knockdown (KD) mast cells. Whereas MCU- and MICU1-KD mast cells show normal proliferation rates and mitochondrial membrane potential, they exhibit slow and reduced cytosolic and mitochondrial Ca2+ elevation after antigen stimulation. Moreover, β-hexosaminidase release induced by antigen was significantly suppressed in MCU-KD cells but not MICU1-KD cells. This suggests that both MCU and MICU1 are involved in mitochondrial Ca2+ uptake in mast cells, while MCU plays a role in mast cell degranulation. Springer Science+Business Media New York, 2015 Calcium nationallicence Degranulation nationallicence Mast cell nationallicence MCU nationallicence Mitochondria nationallicence Furuno Tadahide School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut Shinkai Narumi School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut Inoh Yoshikazu School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut Nakanishi Mamoru School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 215-221 0300-8177 410:1-2<215 2015 410 11010 https://doi.org/10.1007/s11010-015-2554-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2554-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Furuno Tadahide School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut NATIONALLICENCE 700 1- Shinkai Narumi School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut NATIONALLICENCE 700 1- Inoh Yoshikazu School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut NATIONALLICENCE 700 1- Nakanishi Mamoru School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, 464-8650, Chikusa-ku, Nagoya, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 215-221 0300-8177 410:1-2<215 2015 410 11010