Sites of inhibition of mitochondrial electron transport by cadmium

Stefania Miccadei, Aristide Floridi

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Cadmium is an extremely toxic environmental contaminant having a long half-life in humans. The greatest accumulation occurs in the liver and kidneys. Since mitochondria are the most sensitive targets, the effect of cadmium on the oxygen consumption and on the redox state of electron carriers of rat liver mitochondria has been evaluated. Cadmium markedly inhibits uncoupler-stimulated oxidation on various NADH-linked substrates as well as that of succinate. Experiments on specific segments of the respiratory chain showed that cadmium does not inhibit electron flow through cytochrome oxidase, whereas the inhibition of duroquinol oxidation clearly demonstrates an impairment of electron flow through site 2, the ubiquinone-b-cytochrome c1 complex. On the basis of the ability of N,N,N′,N′ tetramethyl-p-phenylendiamine and 2,6-dichlorophenolinindophenol bypasses to relieve the cadmium inhibition of succinate oxidation and on the spectroscopic behaviour of the cytochrome b, the inhibition was found to take place before cytochrome b and, more precisely, between ubisemiquinone and cytochrome bT. Furthermore, the finding that cadmium induces a more oxidized state of cytochrome b in state 1 demonstrates the existence of a second point in which it inhibits electron transfer. Spectroscopic evidence demonstrates that cadmium induces an oxidation of NAD(P)H in mitochondria in states 1 and 4 and prevents the reduction of mitochondrial NAD(P)+ by substrates, thus indicating that the site must be localized between NAD-linked substrates and respiratory chain.

Original languageEnglish
Pages (from-to)159-167
Number of pages9
JournalChemico-Biological Interactions
Volume89
Issue number2-3
DOIs
Publication statusPublished - 1993

Fingerprint

Electron Transport
Cadmium
NAD
Cytochromes b
Mitochondria
Electrons
coenzyme Q10
Oxidation
Succinic Acid
Liver
Cytochromes c1
Substrates
Carrier State
Liver Mitochondrion
Poisons
Electron Transport Complex IV
Cytochromes
Oxygen Consumption
Oxidation-Reduction
Half-Life

Keywords

  • Cadmium
  • Electron transport
  • Inhibition
  • Mitochondria

ASJC Scopus subject areas

  • Toxicology

Cite this

Sites of inhibition of mitochondrial electron transport by cadmium. / Miccadei, Stefania; Floridi, Aristide.

In: Chemico-Biological Interactions, Vol. 89, No. 2-3, 1993, p. 159-167.

Research output: Contribution to journalArticle

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