Mitochondrial Ca2+ uptake with and without the formation of high-Ca2+ microdomains

The mitochondrial Ca2+ uniporter has low affinity for Ca2+, therefore it has been assumed that submicromolar Ca2+ signals cannot induce mitochondrial Ca2+ uptake. The close apposition of the plasma membrane or the endoplamic reticulum (ER) to the mitochondria and the limited Ca2+ diffusion in the cytoplasm result in the formation of perimitochondrial high-Ca2+ microdomains (HCMDs) capable of activating mitochondrial Ca2+ uptake. The possibility of mitochondrial Ca2+ uptake at low submicromolar [Ca2+]c has not yet been generally accepted.Earlier we found in permeabilized glomerulosa, luteal and pancreatic β cells that [Ca2+]m increased when [Ca2+]c was raised from 60 nM to less than 200 nM. Here we report data obtained from H295R (adrenocortical) cells transfected with ER-targeted GFP. Cytoplasmic Ca2+ response to angiotensin II was different in mitochondrion-rich and mitochondrion-free domains. The mitochondrial Ca2+ response to angiotensin II correlated with GFP fluorescence indicating the vicinity of ER. When the cells were exposed to K+ (inducing Ca2+ influx), no correlation was found between the mitochondrial Ca2+ signal and the vicinity of the plasma membrane or the ER. The results presented here provide evidence that mitochondrial Ca2+ uptake may occur both with and without the formation of HCMDs within the same cell.