Reversible depolarization of in situ mitochondria by oxidative stress parallels a decrease in NAD(P)H level in nerve...

Area of Science:

• Neurochemistry
• Mitochondrial Biology
• Oxidative Stress Research

Background:

• Mitochondrial membrane potential (delta(psi)m) is crucial for neuronal function.
• Hydrogen peroxide (H2O2) is known to disrupt cellular processes, including mitochondrial function.
• Previous work indicated H2O2 reduces delta(psi)m in isolated nerve terminals even without proton pump activity.

Purpose of the Study:

• To investigate the role of catalase in reversing H2O2-induced mitochondrial dysfunction.
• To explore the relationship between NAD(P)H levels and mitochondrial membrane potential under oxidative stress.
• To determine the impact of H2O2 on ATP levels and glycolysis in nerve terminals.

Main Methods:

• Measuring mitochondrial membrane potential (delta(psi)m) in isolated nerve terminals.
• Utilizing inhibitors like oligomycin (F0F1-ATPase inhibitor) and rotenone (Complex I inhibitor).
• Assessing NAD(P)H and ATP levels, and the ATP/ADP ratio.

Main Results:

• Catalase reversed the H2O2-induced decrease in delta(psi)m and NAD(P)H levels when F0F1-ATPase was inhibited.
• H2O2 decreased ATP levels and the ATP/ADP ratio, indicating glycolysis inhibition, which was not reversible by catalase.
• The effect of H2O2 on delta(psi)m in the presence of rotenone was not altered by catalase.

Conclusions:

• Catalase can restore mitochondrial membrane potential and NAD(P)H levels compromised by H2O2.
• These findings suggest a significant link between reduced NAD(P)H and the failure of mitochondria to maintain delta(psi)m during oxidative stress.
• H2O2 inhibits glycolysis, but this effect is independent of the mechanisms affecting delta(psi)m reversal by catalase.