Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells

We identified the site of reactive oxygen species production in mitochondria. 3-Nitropropionic acid increased O2− generation in mitochondria respiring on the complex I substrates pyruvate + malate, an effect fully inhibited by rotenone

Attila Bacsi


Scholarcy highlights

  • 3-Nitropropionic acid, an inhibitor of succinate dehydrogenase at complex II of the mitochondrial electron transport chain induces cellular energy deficit and oxidative stressrelated neurotoxicity
  • We recently showed that increasing antioxidant capacity of mitochondria by Bcl-2 overexpression protects PC12 cells from 3-NPA toxicity
  • Release of superoxide anions from mitochondria is the main source of cellular oxidative stress. 3-NPA significantly increases the levels of oxidized hydroethidine, 8hydroxy-2-deoxyguanosine levels, and induces DNA fragmentation in the manganese superoxide dismutase heterozygous mice. 3-NPA causes a corresponding increase in the activities of SOD2 and glutathione peroxidase
  • Cells were loaded with 2 μM H2Et, and placed in a thermo-controlled microscopic chamber and pHadjusted 3-NPA was added
  • Mock-treated cultures were exposed to PBS, substituting an equimolar amount of NaCl for 3-NPA
  • Our results showed that the green fluorescence mediated by H2Et/superoxide reaction products colocalized with MitoTracker red suggesting that mitochondria are the sites of ROS generation
  • These data provide an explanation for the cell typedependent ROS generation and oxidative stress-mediated cellular toxicity of 3-Nitropropionic acid that was not clearly understood previously

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