To assess the role of mitochondrial metabolic competence (MMC) in neuronal aging, quantitative immunohistochemistry of cytochrome oxidase (COX) subunits I (mitochondrial-encoded) and IV (nuclear-encoded) was carried out in the cerebellar cortex of adult and old rats. The optical density (OD) values of the immunostained COX subunits I and IV were measured on an overall area of 75,000 μm2 in the granular and molecular layers of the cerebellar cortex of each animal. In old animals, OD values of subunit I were increased by 35.5 and 34.2% in the molecular and granular layers, respectively, but only the difference found in the latter cerebellar zone was statistically significant (p <0.05%). As regards subunit IV, old animals showed higher, not significant, densitometric values in the molecular (+20.6%) and granular (+26.8%) layers. The present findings sustain that gene expression of COX subunits I and IV appears not to be involved in the well-documented time-related mitochondrial decay. The proper functioning of COX depends on several factors that can affect MMC in the aging cell. In the fully assembled holoenzyme, both the subunits I and IV span the inner mitochondrial membrane. On the basis of these molecular biology data, it is reasonable to suppose that any alteration of the physicochemical features and chemical composition of the mitochondrial membranes reported to occur in aging (e.g., decreased membrane fluidity and cardiolipin content, increased cholesterol/phospholipid molar ratio and free-radical damage, etc.) may significantly affect the proper assembling of the enzyme and, in turn, its activity. Considering the reported significant decline of COX activity with advancing age, our findings further support that an adequate mitochondrial metabolic competence, while including proper nuclear and mitochondrial gene expression of subunits of the respiratory chain, relies on the overall balance among various determinants that can be differently damaged by aging and represent critical causative events responsible for the age-related functional decline of selected mitochondrial populations.
- COX subunit I
- COX subunit IV
- Cytochrome oxidase
- Mitochondrial metabolic competence
- Neuronal aging
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)