Mechanism of the controlling function of mitochondria

Abstract

Liver, heart, brain and tumour-cell mitochondria release into incubation medium two glycolysis-stimulating factors: a lipoprotein “kinasine”, and a nucleotide factor (consisting mainly of ATP and some ADP and NAD). Chemical characteristics and properties of kinasine are outlined. At low ATP concentrations in the medium (not over 1.6·10 −3 M), kinasine stimulates glycolysis while at high ATP concentrations (3.2·10 −3 M) inhibition of glycolysis occurs, kinasine becoming ineffective. When mitochondria contract under the effect of ATP, Mg 2+ or EDTA, they retain kinasine and NAD; swelling, however, as well as anaerobiosis or the effect of 2,4-dinitrophenol, result in release of kinasine and NAD by mitochondria into the medium. An actomyosin-like protein is shown to occur in mitochondria and in the outer membrane of the liver cell. Kinasine is found to activate glycolysis of intact nuclei and nuclear extract. Membrane permeability for kinasine and ATP in tumour mitochondria proves to be independent of their contractility. No actomyosin-like protein could be extracted with Weber's solution from tumour mitochondria. The membrane hypothesis of regulation of glycolysis in the normal living cell and of its impairment in the tumour cell, is outlined.