Interactions of a mitochondrial Ca 2+-binding glycoprotein with lipid bilayer membranes

Abstract

Received 31 May 1974 1. Introduction Attempts to resolve the molecular system for the transport of Ca ‘+ across the mitochondrial membrane have led to the isolation of a glycoprotein with high affinity for Ca’+ [l-3 1. The glycoprotein appears to be associated with the mitochondrial membranes with various degrees of tightness. Part of it is easily solubil- ized into aqueous media by mild hypotonic shocks applied to mitochondria, part of it requires treatment with the glycoprotein-specific chaotropic agent lithium-di-jodosalycilate (LIS) [4]. The chemical and functional properties of the osmotic and LIS-protein are very similar, but one possible explanation for their different dissociability from the membrane environment is their different phospholipid content. The functional properties of the isolated glyco- protein (e.g., affinity for Ca’+, sensitivity to inhibitors, absence from Ca-negative mitochondria, etc.) are closely related to those of the high-affinity Ca2+ binding sites, and of the energy-linked transport of Ca2+, of intact mitochondria. The participation of the glycoprotein in the process of Ca2+ translocation in intact mitochondria seems thus a likely possibility. Whether the glycoprotein acts as a mobile carrier which translocates Ca2+ across the apolar region of the membrane, or whether it forms a tixed, Ca2+-specific tunnel across the entire width of the membrane, is open to question. The highly polar character of the glycoprotein is not per se a sufficient reason to exclude the mobile carrier mechanism: the solubil- ization of highly polar proteins like cytochrome c, or rhodopsin, into apolar solvents has recently been achieved [ $61 and has been shown to depend on the