Long chain fatty acyl-CoA modulation of H(2)O (2) release at mitochondrial complex I.

J Bioenerg Biomembr

Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padua, Italy.

Published: February 2008

AI Article Synopsis

  • - Complex I in mitochondria mainly produces hydrogen peroxide (H2O2), with levels being low during NAD-linked substrate oxidation but high during succinate oxidation due to reverse electron flow.
  • - This H2O2 production is considered physiological, occurring even at low succinate concentrations and in the presence of NAD substrates in heart and rat brain mitochondria.
  • - Long-chain fatty acyl-CoAs inhibit succinate-dependent H2O2 release, and this inhibition is influenced by their unbound form and is independent of their oxidation, with effects being modulated by compounds like carnitine and malonyl-CoA.

Article Abstract

Complex I is responsible for most of the mitochondrial H(2)O(2) release, low during the oxidation of the NAD linked substrates and high during succinate oxidation, via reverse electron flow. This H(2)O(2) production appear physiological since it occurs at submillimolar concentrations of succinate also in the presence of NAD substrates in heart (present work) and rat brain mitochondria (Zoccarato et al., Biochem J, 406:125-129, 2007). Long chain fatty acyl-CoAs, but not fatty acids, act as strong inhibitors of succinate dependent H(2)O(2) release. The inhibitory effect of acyl-CoAs is independent of their oxidation, being relieved by carnitine and unaffected or potentiated by malonyl-CoA. The inhibition appears to depend on the unbound form since the acyl-CoA effect decreases at BSA concentrations higher than 2 mg/ml; it is not dependent on DeltapH or Deltap and could depend on the inhibition of reverse electron transfer at complex I, since palmitoyl-CoA inhibits the succinate dependent NAD(P) or acetoacetate reduction.

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http://dx.doi.org/10.1007/s10863-008-9126-1DOI Listing

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