Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions

Abstract

1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed.

In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague–Dawley rat

“…The molecular mechanisms for the formation of these organotin-induced lipid inclusions remain enigmatic. It could be due to the potent inhibition of mitochondrial oxidative phosphorylation by TBT [35][36][37], accumulation of acetyl-CoA, and inhibition of fatty acid transport to the mitochondria, hence its accumulation in the cytoplasm [38].…”

The interaction of tributyllead with lysosomes from rat liver

“…R5alkyl) with the membrane and in particular the toxicity vacuolar pump. In this case, the mechanism of Cl / OH 2 of trialkyllead compounds [1][2][3]. This mechanism proexchange cannot be proposed since Cl is absent from the poses that trialkylmetals enter mitochondria as R MCl medium.…”

“…In the last few years the study of the interactions of In order to confirm this mechanism, in this paper we trialkyl metals with the biological structures have received have studied the interactions of Bu PbCl with lysosomes. 3 more and more attention since these compounds are Like mitochondria, lysosomes are sensitive to the presence involved in many problems of environmental concerns of uncouplers, but, differently from mitochondria, they do [1][2][3][4][5][6][7][8][9][10][11]. Therefore, the behaviour and the toxic effects of not produce ATP, but utilise ATP to pump protons in the trialkylmetal compounds have been largely investigated in inner compartment.…”

“…somes are less complex systems than mitochondria since The molecular interactions of R PbCl with mitochondria the respiratory chain which interferes with trialkyllead 3 have been largely studied [1][2][3] and a model has been compounds and proteic channels pore [12] are absent. proposed which suggests that these compounds act as Therefore, lysosomes are a good test to confirm the 2 2 Cl / OH exchanger: leadtrialkyls enter the mitochondrial already proposed uncoupling mechanism.…”

The interaction of methylmercury with lysosomes from rat liver

“…1, trace d). e) Presence of an antiporter system, such as an OH ( / Cl ( exchanger [33,34]. This situation has been proposed as an explanation for the toxicity of many organometal compounds, such as alkyl 3 SnCl and alkyl 3 PbCl [33,34].…”