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.