Mitochondrial calcium plays a critical role in diverse cellular processes. Normal mitochondrial calcium uptake enhances energy production and facilitates metabolism. However, in pathological conditions, mitochondrial calcium overload promotes cell death. Therefore, mitochondrial calcium uptake should be under tight regulation for mitochondrial and cellular homeostasis. Recently, mitochondrial calcium uniporter (MCU) was identified as the transporter for rapid mitochondrial calcium uptake. Although there are many assumptions about the physiological roles of MCU, its functions and interactions in vivo are largely unknown. In this study, I generated MCU deletion fly line, which I named MCU52, with loss of MCU gene expression and impaired mitochondrial calcium uptake. I tried to reveal the physiological role of MCU in Drosophila by characterizing the mutant phenotypes. I found that MCU52 mutants were more resistant to oxidative stress conditions and defective in locomotion while normal in organism development, mitochondrial dynamics, ATP production, and basal metabolism. Strikingly, in oxidative stress conditions, survival of the MCU52 mutants was greater than that of the control. Consistently, MCU52 mutants showed reduced cell death after direct H2O2 treatment to the larval tissues including the brain and muscles. Collectively, these results demonstrate that MCU contributes to cell death induction upon oxidative stress by sensitizing the cells to mitochondrial calcium overload.
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