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The study characterized changes in mitochondrial function in response to six months CR in rats, measuring bioenergetic parameters, redox balance and calcium homeostasis. CR promoted an increase in succinate-supported mitochondrial oxygen consumption rates. While CR prevents mitochondrial reactive oxygen species production in many tissues, we found that mitochondrial H2O2 release was enhanced in a succinate-dependent manner in the kidney. Instead, increased mitochondrial calcium uptake rates in CR kidneys correlate with a loss of MICU2, an MCU modulator. Interestingly, MICU2 is also modulated by CR in the liver, suggesting it has a broader diet-sensitive regulatory role in controlling mitochondrial calcium homeostasis. The results highlight CR's organ-specific bioenergetic, redox, and ionic transport effects, with some unexpected harmful impacts on the kidney.
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