Mitochondrial reactive oxygen species in physiology and disease

Mitochondrial reactive oxygen species (mROS) are routinely produced at several sites within the organelle. The balance in their formation and elimination is maintained by a complex and robust antioxidant system. mROS may act as second messengers and regulate a number of physiological processes, such as insulin signaling, cell differentiation and proliferation, wound healing, etc. Nevertheless, when a sudden or sustained increase in ROS formation is not efficiently neutralized by the endogenous antioxidant defense system, the detrimental impact of high mROS levels on cell function and viability eventually results in disease development. In this review, we will focus on the dual role of mROS in pathophysiology, emphasizing the physiological role exerted by a regulated mROS production/elimination, and discussing the detrimental effects evoked by an imbalance in mitochondrial redox state. Furthermore, we will touch upon the interplay between mROS and Ca²⁺ homeostasis.