Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review)

Mitochondria and chloroplasts represent endosymbiotic models of complex organelle development, driven by intense evolutionary pressure to provide exponentially enhanced ATP-dependent energy production functionally linked to cellular respiration and photosynthesis. Within the realm of translational medicine, it has become compellingly evident that mitochondrial dysfunction, resulting in compromised cellular bioenergetics, represents a key causative factor in the etiology and persistence of major diseases afflicting human populations. As a pathophysiological consequence of enhanced oxygen utilization that is functionally uncoupled from the oxidative phosphorylation of ADP, significant levels of reactive oxygen species (ROS) may be generated within mitochondria and chloroplasts, which may effectively compromise cellular energy production following prolonged stress/inflammatory conditions. Empirically determined homologies in biochemical pathways, and their respective encoding gene sequences between chloroplasts and mitochondria, suggest common origins via entrapped primordial bacterial ancestors. From evolutionary and developmental perspectives, the elucidation of multiple biochemical and molecular relationships responsible for errorless bioenergetics within mitochondrial and plastid complexes will most certainly enhance the depth of translational approaches to ameliorate or even prevent the destructive effects of multiple disease states. The selective choice of discussion points contained within the present review is designed to provide theoretical bases and translational insights into the pathophysiology of human diseases from a perspective of dysregulated mitochondrial bioenergetics with special reference to chloroplast biology.