Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats

FEBS Lett. 1997 Jun 30;410(2-3):467-9. doi: 10.1016/s0014-5793(97)00638-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • DNA, Mitochondrial / metabolism
  • Enzyme Inhibitors / pharmacology
  • Male
  • Mitochondria / metabolism*
  • Multienzyme Complexes / metabolism
  • NAD / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors*
  • NADH, NADPH Oxidoreductases / metabolism
  • Neuroglia / cytology
  • Neurons / cytology
  • Rats
  • Rats, Wistar
  • Rotenone / pharmacology*
  • Synapses

Substances

  • DNA, Mitochondrial
  • Enzyme Inhibitors
  • Multienzyme Complexes
  • Rotenone
  • NAD
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • NAD(P)H Dehydrogenase (Quinone)