Decay of mitochondrial metabolic competence in the aging cerebellum
C. Bertoni-Freddari, P. Fattoretti, B. Giorgetti, M. Solazzi, M. Balietti
Neurobiology of Aging Laboratory, INRCA Research Department, Via Birarelli 8, 60121 Ancona, Italy
Cytochrome oxidase (COX) activity, selectively evidenced by
preferential diaminobenzidine cytochemistry, has been measured by
computer-assisted morphometric methods in the cerebellar cortex of
adult and old rats. We calculated the ratio (R) between the area of the
precipitate due to the cytochemical reaction and the overall area of
each mitochondrion. The value of R is reported to provide information
on the fraction (%) of the inner mitochondrial membrane actively
involved in adenosine triphosphate (ATP) provision. Thus, since COX is
the terminal enzyme of the mitochondrial respiratory chain, R can be
considered a reliable index of the mitochondrial metabolic competence
(MMC), i.e. the capacity of each organelle to provide ATP. The data
from each animal were ordered by increasing values of mitochondrial
area, then they were divided into quartiles. While in adult rats we
documented an inverse correlation between mitochondrial size and R
values (r = -0.905), in old animals we found increasing values of R as
the mitochondrial area increases (r =0.561). Paired-quartile
comparisons of the R values from adult and old animals documented a
marked age-related impairment of MMC in small (I quartile: -31.6%) and
medium-sized (II quartile: -26.4; III quartile: -16.4) mitochondria,
while large organelles showed the lowest age-related decrease (IV
quartile: -3.0%). Mitochondrial decrease in number and increase in size
are consistently reported as a general trend in old organisms.
Mitochondrial enlargement is supposed to constitute a compensating
reaction to the numeric loss since it extends the inner membrane area
potentially involved in the respiratory chain. This compensation has
been reported to be due to an increased complement of oversized
mitochondria in discrete cellular or tissue compartments, however it is
still debated whether these enlarged organelles are capable of
providing adequate amounts of ATP according to their enlarged size. By
matching quantitative preferential cytochemistry of COX and classical
morphometric procedures, the present findings support that in adulthood
as well as in aging the complement of oversized mitochondria appears to
represent a weak compensating reaction since in both these conditions
their R value is about 0.28 vs. 0.39 and 0.26 of the small-sized
organelles in adult and old animals, respectively. Conceivably, our
results support that a marked dysfunction of small and medium-sized
mitochondria contributes to the significant decay of energy metabolism
well documented in physiological aging.
Key words:
Mitochondrial metabolic competence, cerebellum, mitochondrial size, megamitochondria, cytochrome oxidase activity
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