Ultrastructural alteration of the mitochondrial electron transport chain involving electron leak possible basis of “respiratory impairment” in certain tumors

Abstract

It is proposed that the lower respiratory rates found in certain tumor mitochondria as compared to that in corresponding non-neoplastic tissue results initially from the considerable alteration or deletion of the mechanochemical effector system which is responsible for the swelling and contraction of mitochondria. The effector system, which is membranelocalized, is linked to the respiratory chain in a position adjacent to the coupling sequence which is responsible for phosphorylation. The considerable loss or disappearance of both the “high amplitude” swelling and contraction functions in tumor mitochondria indicate severe alteration or deletion of the effector system. Since it is well-established that the respiratory multienzyme assemblies in the membrane are lipoid coated (for the insulation of electron transport from the aqueous phase), the alteration or deletion of the effector system cannot fail to bring about a break-up of the lipoid coating; this break-up is possibly compounded by the well-known alterations of fatty acid, phospholipid and cholesterol metabolism in tumors. The working hypothesis is developed that, because of electron leak through this lesion(s), a portion of the electron flux resulting from substrate dehydrogenation does not reach the terminal acceptor, oxygen, although the rate of dehydrogenation may remain unaltered; hence, decrease of the respiratory rate. Corollaries to this situation are analyzed.