Abstract
Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly increases FtMt expression in the murine heart. FtMt gene disruption decreased the exhaustion exercise time and altered heart morphology with severe cardiac mitochondrial injury and fibril disorganization. The number of apoptotic cells as well as the levels of apoptosis-related proteins was increased in the FtMt(-/-) mice, though the ATP levels did not change significantly. Concomitant to the above was a high 'uncommitted' iron level found in the FtMt(-/-) group when exposed to acute exhaustion exercise. As a result of the increase in catalytic metal, reactive oxygen species were generated, leading to oxidative damage of cellular components. Taken together, our results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of mitochondria to cardiac injury via oxidative stress.