Cytochrome c oxidase and its role in neurodegeneration and neuroprotection.

摘要: A hallmark of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s stroke is a malfunction mitochondria including cytochrome c oxidase (COX), the terminal enzyme complex respiratory chain. COX ascribed key role based on mainly two regulatory mechanisms. These are expression isoforms binding specific allosteric factors to nucleus-­encoded subunits. characteristics represent unique feature compared with other chain complexes. Additional mechanisms, posttranslational modification, substrate availability, feedback inhibition by products reaction, control activity in way. In many tissues cell types, represents rate-limiting which further emphasizes impact regulation central site for regulating energy metabolism oxidative stress. Two best-analyzed mechanisms date its indirect product ATP subunit IV isoforms. This requires isoform IV-1. At high ATP/ADP ratios, ADP exchanged at matrix side IV-1 leading an activity, thus enabling sense level adjust synthesis demand. However, under hypoxic, toxic, degenerative conditions, IV-2 up-regulated complex. switch causes abolition consequently loss sensing level. Thus, increased higher levels neural cells independently cellular Concomitantly, ROS production increased. pathological provided meet demand, but expense elevated mechanism explains functional relevance sensing, production, stress levels. This, turn, affects function, signaling, ­survival. crucial factor etiology, progression, prevalence numerous human diseases important target developing diagnostic therapeutic tools against those diseases.