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Updated: Dec 14, 2025

Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
Cyclophilin D counterbalances mitochondrial calcium uniporter-mediated brain mitochondrial calcium uptake
Bei Zhang1, Kun Jia1, Jing Tian1
1Department of Biological Sciences, University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX, 75080, USA.
Abstract:
Mitochondria play an essential role in maintaining intraneuronal calcium homeostasis. Mitochondrial calcium uniporter (MCU) is a determined major brain mitochondrial calcium entry pathway. Activated MCU-mediated mitochondrial calcium overloading has been linked with brain mitochondrial pathology in disease conditions. Cyclophilin D (CypD)-mediated mitochondrial permeability transition (mPT) favors mitochondrial calcium efflux. The physiological function of CypD-mediated mPT has received increasing recognition. However, the regulatory role of CypD-mediated mPT in brain mitochondrial calcium dynamics in response to mitochondrial calcium accumulation via MCU has not been comprehensively studied. Here, by adopting purified brain mitochondria, we have determined an effect of CypD and CypD-mediated mPT against mitochondrial calcium overloading. In addition, blockade of CypD pharmaceutically or genetically blunts brain mitochondrial MCU's sensitivity to its inhibitor. Therefore, our findings suggest that CypD-mediated mPT is a mitochondrial compensatory response to MCU-mediated excess mitochondrial calcium accumulation. Moreover, CypD may potentially modulate MCU function in calcium-stressed mitochondria.
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