Effects of polyamines on mitochondrial Ca2+ transport

Mammalian mitochondria are able to enhance Ca2+ accumulation in the presence of polyammes by activating the saturable systems of Ca2+ inward transport and buffering extramitochondrial Ca2+ concentrations to levels similar to those in the cytosol of resting cells. This effect renders them responsive to regulate free Ca2+ concentrations in the physioloical range. The mechanism involved is due to a rise in the affinity of the Ca2+ transport system, induced by polyamines, most probably exhibiting allosteric behaviour. The regulatory site of this mechanism is the so-called S-1 binding site of polyamines, which operates in physiological conditions and is located in the energy well between the two peaks present in the energy profile of mitochondrial spermine transport. Spermine is bidirectionally transported across teh inner membrane by cycling, in which influx and efflux are driven by electrical and pH gradients, respectively. Most probably, polyamine affects the Ca2+ transport system when it acts from the outside-that is, in the direction of its uniporter channel, in order to reach the S-1 site. Important physiological functions are related to activation of Ca2+ transport systems by polyamines and their interactions with the S-1 site. These functions include a rise in the metabolic rate for energy supply and modulation of mitochondrial permeability transition induction, with consequent effects on the triggering of the apoptotic pathway. (C) 2004 Elsevier B.V. All rights reseved.