Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

Post-translational modifications based on redox reactions “switch on-off” the biological activity of different downstream targets, modifying a myriad of processes and providing an efficient mechanism for signaling regulation in physiological and pathological conditions. Such modifications depend on the generation of redox components, such as reactive oxygen species and nitric oxide. Therefore, as the oxidative or nitrosative milieu prevailing in the reperfused heart is determinant for protective signaling, in this review we defined the impact of redox-based post-translational modifications resulting from either oxidative/nitrosative signaling or oxidative/nitrosative stress that occurs during reperfusion damage. The role that cardioprotective conditioning strategies have had to establish that such changes occur at different subcellular levels, particularly in mitochondria, is also presented. Another section is devoted to the possible mechanism of signal delivering of modified proteins. Finally, we discuss the possible efficacy of redox-based therapeutic strategies against reperfusion damage.