Abstract
A computer-assisted morphometric investigation of cytochrome oxidase (COX) activity, selectively evidenced by preferential diaminobenzidine cytochemistry, has been carried out on synaptic mitochondria in the cerebellar cortex of adult and old rats. The ratio (R) of the area of the cytochemical precipitate (CPA) to the overall area of each mitochondrion (MA) was calculated. R refers to the fraction of the inner mitochondrial membrane actively involved in cellular respiration, thus its quantitative estimation constitutes a reliable index of the mitochondrial metabolic competence (MMC). In adult rats a significant negative correlation between MA and R values was found, while in old animals there was just a positive trend. Paired-quartile comparisons of R values showed a significant age-related decrease in small and medium-sized mitochondria, whereas the lowest and not significant age-related reduction was found in oversized organelles. A paired decrease in number and increase in size is reported to be a general trend for mitochondria during aging, but oversized organelles, according to their low R value, constitute a scanty, though functional, compensating reaction. Thus, the present findings support the argument that the currently reported age-related cellular metabolic decay appears to rely both on the decline in MMC of the small and medium-sized mitochondria, and on their specific reduction in number. This novel result is of biological relevance since it is largely the small and medium-sized mitochondria that are required for the provision of adequate amounts of ATP for actual cellular performance, while the significantly enlarged organelles are thought to represent an intermediate ultrastructural feature in mitochondrial genesis and/or remodelling.
Similar content being viewed by others
References
Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurol Sci 23:298–304
Bereiter-Hahn J (1990) Behaviour of mitochondria in the living cell. Int Rev Cytol 122:1–63
Bertoni-Freddari C, Fattoretti P, Casoli T, Spagna C, Meier-Ruge W, Ulrich J (1993) Morphological plasticity of synaptic mitochondria during aging. Brain Res 628:193–200
Bertoni-Freddari C, Fattoretti P, Casoli T, Di Stefano G, Solazzi M, Meier-Ruge W (2001) Quantitative cytochemical mapping of mitochondrial enzymes in rat cerebella. Micron 32:405–410
Bertoni-Freddari C, Fattoretti P, Paoloni R, Caselli U, Giorgetti B, Solazzi M (2003) Inverse correlation between mitochondrial size and metabolic competence: a quantitative cytochemical study of cytochrome oxidase activity. Naturwissenschaften 90:68–71
Bertoni-Freddari C, Fattoretti P, Giorgetti B, Solazzi M, Balietti M, Meier-Ruge W (2004) Role of mitochondrial deterioration in physiological and pathological brain aging. Gerontology 50:187–192
Coggeshall RE, Lekan HA (1996) Methods for determining numbers of cells and synapses: a case for more uniform standard review. J Comp Neurol 364:6–15
Collins TJ, Berridge MJ, Lipp P, Bootman MD (2002) Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J 21:1616–1627
Hanson BJ, Carrozzo R, Piemonte F, Tessa A, Robinson BH, Capaldi RA (2001) Cytochrome c oxidase-deficient patients have distinct subunit assembly profiles. J Biol Chem 276:16296–16301
Masoro EJ (1996) The biological mechanism of aging: is it still an enigma? Age 19:141–145
Seligman AM, Karnovsky MJ, Wasserkrug HL, Hanker JS (1968) Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerising osmiophilic reagent, diaminobenzidine (DAB). J Cell Biol 38:1–14
Taanman JW (1997) Human cytochrome c oxidase: structure, function, and deficiency. J Bioenerg Biomembr 29:151–163
Walter PB, Beckman KB, Ames BN (1999) The role of iron and mitochondria in aging. In: Cadenas E, Packer L (eds) Understanding the process of aging: the role of mitochondria, free radicals and antioxidants. Marcel Dekker, New York, pp 203–227
Wong-Riley MTT (1989) Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trend Neurosci 12:94–101
Acknowledgements
The experiments performed in this study comply with current Italian laws.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bertoni-Freddari, C., Fattoretti, P., Giorgetti, B. et al. Age-related decline in metabolic competence of small and medium-sized synaptic mitochondria. Naturwissenschaften 92, 82–85 (2005). https://doi.org/10.1007/s00114-004-0591-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00114-004-0591-z