Effects of polyamines on mitochondrial Ca~(2+) transport

摘要

Mammalian mitochondria are able to enhance Ca~(2+) accumulation in the presence of polyamines by activating the saturable systems of Ca~(2+) inward transport and buffering extramitochondrial Ca~(2+) 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 Ca~(2+) 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 Ca~(2+) 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 Ca~(2+) 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.