Energy coupling and extramitochondrial electron transport in slices of Morris hepatoma 3924A

T. Galeotti, E. D'Amico, E. Marchese, R. Bompiani, T. Terranova, M. Russo

Research output: Contribution to journalArticlepeer-review

Abstract

The study of the respiration of solid tumours performed with slice preparations may provide opportunities to evaluate the mitochondrial energy efficiency in a more suitable manner than by using isolated mitochondria. Moreover, such an experimental approach affords a method for estimating at which extent systems of extramitochondrial electron transport can contribute to the total oxygen consumption of the whole cell. In this work we have studied an experimental tumour of the rat, the Morris hepatoma 3924A. Experiments have been also carried out comparatively with rat liver of the ACI/T and Wistar strains. The endogenous respiration of hepatoma slices was stimulated by 27% by 2,4-dinitrophenol and inhibited by 47% by oligomycin. The oligomycin inhibition was not completely released by 2,4-dinitrophenol. A similar behaviour is shown by rat-liver slices. Succinate, but not the NAD-linked substrates, enhanced the endogenous respiration of hepatoma slices. A 17% inhibition by ouabain of the respiration in the presence of glucose was observed in hepatoma slices preincubated 120 min at 1°. Electron microscopic examination of tumour slices showed that mitochondria are in the orthodox conformation. They changed to the condensed conformation following inhibition of respiration at 1°; at 38° they underwent transition to the orthodox conformation. Rotenone, antimycin A and cyanide inhibited the endogenous respiration of hepatoma slices by 85-90% and that of rat liver slices (ACI/T strain) by 57, 68, and 74%, respectively. Treatment of rats of the Wistar strain with phenobarbital did not modify the endogenous respiration of rat-liver slices. However, the respiration was stimulated by 15-20% in the presence of aminopyrine, and inhibited by 48.5% by antimycin A and by 30% by antimycin A plus aminopyrine. Phenobarbital administration to tumour-bearing rats of the ACI/T strain did not influence the tumour respiration. These results provide evidence that the respiration of the hepatoma 3924 A slices is coupled to energy conservation reactions. They further suggest that mitochondria within the slices are in a state intermediate between States 3 and 4. The inhibitor-insensitive oxygen consumption may be ascribed to the operation of electron transport pathways located in membrane systems of the extramitochondrial compartment of the cell.

Original languageEnglish
Pages (from-to)37-50
Number of pages14
JournalZeitschrift für Krebsforschung und Klinische Onkologie
Volume81
Issue number1
DOIs
Publication statusPublished - Jan 1974

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

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