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Updated: May 3, 2026

Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
Mcu regulates bone formation via mitochondrial calcium uptake and lineage allocation
Suji Kim1,2,3,4, Hanna Jeong1,3,4, Tue Nguyen Hoang1,2,3,4
1Organelle Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
None:
The mitochondrial calcium uniporter (Mcu) mediates calcium influx into the mitochondrial matrix, playing an essential role in cellular energy metabolism and survival. Although Mcu has been studied in various physiological contexts, its role in skeletal homeostasis remains poorly understood. Here we investigate how Mcu deficiency affects osteoblast differentiation and bone formation under aging-related stress. Using an inducible whole-body Mcu-knockout mouse model, we found that Mcu deletion resulted in impaired mitochondrial calcium uptake, reduced oxidative phosphorylation, fragmented mitochondrial morphology and decreased expression of osteogenic genes, leading to defective osteogenesis. Concurrently, adipogenic markers were elevated in Mcu-deficient bone marrow cells, indicating altered mesenchymal lineage commitment. Mechanistically, Mcu-deficient cells exhibited enhanced TGF-β signaling and reduced BMP/Wnt pathway activity. In vivo, inducible whole-body Mcu-knockout mice exhibited reduced trabecular bone volume and density while maintaining normal skeletal growth. Pharmacological modulation of mitochondrial calcium influx using kaempferol enhanced osteogenic differentiation and mitochondrial respiration in wild-type, but not Mcu-deficient, cells. Consistently, analysis of publicly available human datasets revealed age- and osteoporosis-associated downregulation of MCU expression in bone tissues. These findings suggest that Mcu regulates bone formation by controlling mitochondrial calcium uptake and mesenchymal lineage allocation. Targeting mitochondrial calcium signaling may offer novel therapeutic strategies for age-related skeletal disorders.
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