Energy-Redox Axis in Mitochondria Interconnection of Energy-Transducing Capacity and Redox Status

Mitochondrial dysfunction is implicated in multiple pathological conditions, particularly those involving metabolically active tissues such as the brain, liver, and heart. Mitochondrial dysfunction is manifested by not only deficits in their energy transducing capacity, but also through perturbations to their redox homeostasis in terms of increased generation of O2 – and H2O2, altered NADPH and GSH status, and increased macromolecule oxidative modification. The interconnectivity between these energy- and redox-related events is established by nicotinamide nucleotide transhydrogenase (NNT) and the inhibitory oxidation of mitochondrial bioenergetic enzymes. The energy-redox axis is, therefore, proposed as a unique perspective that describes concerted alterations in mitochondrial bioenergetic and redox-modulating properties under various circumstances. Moreover, the energy-redox axis is actively involved in the communications between mitochondria and the rest of the cell by an array of energy- and redox-sensitive kinase signaling and transcriptional pathways. Through these pathways, the energy-redox axis coordinates with the dynamic remodeling and quality control mechanisms of mitochondria for optimized metabolic and redox functions.