Control of oxidative phosphorylation by Complex I in rat liver mitochondria: implications for aging.
We compared NAD-dependent state 4 and state 3 respiration, NADH oxidation and Complex I specific activity in liver mitochondria from 4- and 30-month-old rats. All the activities examined were significantly decreased with aging. In both groups of animals, the flux control coefficients measured by rotenone titration indicated that Complex I is largely rate controlling upon NADH aerobic oxidation while, in state 3 respiration, it shares the control with other steps in the pathway. Moreover, we observed a trend wherein flux control coefficients of Complex I became higher with age. This indication was strengthened by examining the rotenone inhibition thresholds showing that Complex I becomes more rate controlling, over all the examined activities, during aging. Our results point out that age-related alterations of the mitochondrial functions are also present in tissues considered less prone to accumulate mitochondrial DNA mutations.
Ventura
Barbara
B
Dipartimento di Biochimica G. Moruzzi, Università di Bologna, Via Irnerio 48, 40126, Bologna, Italy.
Genova
Maria Luisa
ML
Bovina
Carla
C
Formiggini
Gabriella
G
Lenaz
Giorgio
G
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000378:metabolism; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012402:Rotenone; D009243:NAD; D010088:Oxidoreductases; C022691:succinate oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III