Regulation of mitochondrial metabolism through changes in matrix volume

Abstract

Introduction It has been known for many years thal de-energized mitochondria behave as perfect osmometers; as the osmolarity of the medium is altere'd, the matrix volume changes to equilibrate the osmotic pressure across the inner membrane [ 11. Indeed, the folding of the inner membrane into cristae allows mitochondria to swell to many times their original volume without rupturing. Under physiological conditions, however, mitochondria maintain their matrix volume within narrow limits through the operation of volume regulatory mechanisms that move K + and compensating anions in or out of the mitochondria. Research carried out in this laboratory during the past ten years has indicated that hormones acting on the cell surface are able to attenuate this regulatory mechanism and so cause small ( 10-3OYo) increases in the mitochondrial volume which have profound effects on mitochondrial metabolism. I have proposed that, in the liver, such volume-mediated changes in mitochondrial metabolism play a critical role in the stimulation of respiration, nitrogen metabolism and gluconeogenesis by hormones such as glucagon and adrenaline. This article provides a brief review of the work supporting this assertion and considers how it may relate to the current interest in the effect of cell volume on the regulation of metabolism. For more detailed reviews, the reader is directed elsewhere [ 1 , q .