Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats.
We investigated NADH oxidation in non-synaptic and synaptic mitochondria from brain cortex of 4- and 24-month-old rats. The NADH oxidase activity was significantly lower in non-synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone-binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.
Genova
M L
ML
Department of Biochemistry, University of Bologna, Italy.
Bovina
C
C
Marchetti
M
M
Pallotti
F
F
Tietz
C
C
Biagini
G
G
Pugnaloni
A
A
Viticchi
C
C
Gorini
A
A
Villa
R F
RF
Lenaz
G
G
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology*; D013569:Synapses
D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D012402:Rotenone; D009243:NAD; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone)