Mitochondria as all-round players of the calcium game

Although it has been known for over three decades that mitochondria are endowed with a complex array of Ca2+ transporters and that key enzymes of mitochondrial metabolism are regulated by Ca2+, the possibility that physiological stimuli that raise the [Ca2+] of the cytoplasm could trigger major mitochondrial Ca2+ uptake has long been considered unlikely, based on the low affinity of the mitochondrial transporters and the limited amplitude of the cytoplasmic [Ca2+] rises. The direct measurement of mitochondrial [Ca2+] with highly selective probes has led to a complete reversion of this view, by demonstrating that, after cell stimulation, the cytoplasmic Ca2+ signal is always paralleled by a much larger rise in [Ca2+] in the mitochondrial matrix. This observation has rejuvenated the study of mitochondrial Ca2+ transport and novel, unexpected results have altered long-standing dogmas in the field of calcium signalling. Here we focus on four main topics: (i) the current knowledge of the functional properties of the Ca2+ transporters and of the thermodynamic constraints under which they operate; (ii) the occurrence of mitochondrial Ca2+ uptake in living cells and the key role of local signalling routes between the mitochondria and the Ca2+ sources; (iii) the physiological consequences of Ca2+ transport for both mitochondrial function and the modulation of the cytoplasmic Ca2+ signal; and (iv) evidence that alterations of mitochondrial Ca2+ signalling may occur in pathophysiological conditions

Correlation between human platelet cytoplasmic membrane outer leaflet fluidity, Na+/H+ exchanger activity and aging

Abstract A cross-sectional survey was undertaken to study the aging effect on platelet cytoplasmic membrane outer leaflet fluidity and Na+/H+ antiporter activity, and to investigate the relative influence of membrane order and age on the Na+/H+ exchanger. The study population consisted of 19 healthy subjects (age range 22–83 years, mean age 48.5 ± 16.5 years; 12 females and 7 males). Washed platelets were used as neuronal models and as eventually contributing to brain pathology by aberrant secretion of their granule content. A significant positive correlation (r = 0.48,p < 0.05) was found between age and the membrane structural order, according to a second-degree equation. Sewall-Wright path coefficient analysis revealed that the age influence on Na+/H+ exchanger activity was unimportant (0.18), but those of cytoplasmic membrane outer leaflet fluidity and mean platelet volume were strong and positive (0.51 and 0.54, respectively). Women presented a marked standard deviation in the countertransporter results. In conclusion, decreased membrane outer leaflet fluidity and unchanged Na+/H+ antiporter activity may contribute to the process of normal brain aging