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 language | English |
|---|---|
| Pages (from-to) | 159-167 |
| Number of pages | 9 |
| Journal | Chemico-Biological Interactions |
| Volume | 89 |
| Issue number | 2-3 |
| DOIs | |
| Publication status | Published - 1993 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Sites of inhibition of mitochondrial electron transport by cadmium
AU - Miccadei, Stefania
AU - Floridi, Aristide
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - Cadmium
KW - Electron transport
KW - Inhibition
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=0027729382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027729382&partnerID=8YFLogxK
U2 - 10.1016/0009-2797(93)90006-K
DO - 10.1016/0009-2797(93)90006-K
M3 - Article
C2 - 8269544
AN - SCOPUS:0027729382
VL - 89
SP - 159
EP - 167
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
SN - 0009-2797
IS - 2-3
ER -