There is ample evidence to suggest that a dramatic decrease in mitochondrial Ca2+ retention may contribute to the cell death associated with stroke, excitotoxicity, ischemia and reperfusion, and neurodegenerative diseases. Mitochondria from all studied tissues can accumulate and store Ca2+, but the maximum Ca2+ storage capacity varies widely and exhibits striking tissue specificity. There is currently no explanation for this fact. Precipitation of Ca2+ and phosphate in the mitochondrial matrix has been suggested to be the major form of storage of accumulated Ca2+ in mitochondria. How this precipitate is formed is not known. The molecular identity of almost all proteins involved in Ca2+ transport, storage and formation of the permeability transition pore is also unknown. This review summarizes studies aimed at identifying these proteins, and describes the properties of a known mitochondrial protein that may be involved in Ca2+ transport and the structure of the permeability transition pore.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2010.07756.x

The molecular identity of the mitochondrial Ca2+ sequestration system.

WE have described a glycoprotein isolated from various mitochondria1, which binds Ca2+ with a dissociation constant of the same order of magnitude as the Km for Ca2+ transport2,3. This and other observations, including the effects of known Ca2+ transport inhibitors4,5 suggest that the protein is involved in the carrier mechanism for the transport of calcium in mitochondria. We have concluded that even passive efflux of Ca2+ from mitochondria requires the glycoprotein to be associated with the membrane6, and we consider this to be strong evidence that the passage of Ca2+ across the mitochondrial membrane requires the mediation of a transport system including the glycoprotein. We have sought to confirm these conclusions by immunological methods.

Specific inhibition of mitochondrial Ca2+ transport by antibodies directed to the Ca2+-binding glycoprotein.

Summary

1. The nucleus has a distinctive carbohydrate chemistry, the main features of which are the lack of glycosphingolipid, the high density of carbohydrate per unit area of nuclear membrane, the presence of glycosaminoglycan in the nuclear matrix and possibly the nuclear membranes, and the existence of glycosylated non-histone proteins.



2. The nucleus has considerable autonomy in its metabolism of glycosaminoglycan and has a capacity for glycosyl transfers involving glycosyl dolichyl phosphates and pyrophosphates. This latter activity probably resides in the nuclear membranes.



3. The soluble fraction of the nucleoplasm contains the total cellular CMP-sialic-acid synthetase and, hence, all sialic acid metabolism passes through the nucleus, which may have a regulatory role. Uncertainty remains as to the sialic acid content of the glycoproteins of the nucleus and it is likely to vary between cell types.



4. Malignancy is associated with several alterations in the glycosylation of nuclear membranes, including increased levels of sialic acids in the glycoproteins of the inner nuclear membrane: changes in glycosylation of the matrix and chromatin are not yet well defined. In malignancy, some nuclear glycoproteins may possibly appear in other cellular membranes.

Nuclear glycoconjugates and their relation to malignancy.

Mitochondrial function is highly dependent upon the concentrations of cations within the various compartments of this organelle. Utilizing variants of the pyroantimonate precipitation method, we have undertaken to localize cations, particularly calcium, in isolated mitochondria. Precipitated cations were present in two major compartments: 1) within the intracristal space and 2) in the matrix, frequently in association with the matrix face of cristal membranes. Precipitated cations were abundant in mitochondrial samples fixed with most pyroantimonate-containing fixatives, but were usually absent in samples fixed in phosphate-buffered, pyroantimonate-containing fixative solutions. Atomic absorption spectroscopy demonstrated that Ca2+ added to mitochondrial suspensions prior to fixation was retained in the mitochondrial pellet if 0.1 M collidine was present as the fixative buffer. When the same concentration of phosphate-buffered pyroantimonate-osmium fixative was employed, however, much of the added Ca2+ wa...

Distribution of mitochondrial calcium: pyroantimonate precipitation and atomic absorption spectroscopy.

One of the most intensively investigated fields of biological research nowadays is membrane structure and function.The reason for this great interest resides in the great number of biological functions connected with these microscopic structures. It is not appropriate to recall here all the concepts which have developed in this area since some decades (see for a recent review 1). The most generally accepted structure today is that illustrated by Singer (2) and referred to as fluid-mosaic model. In the model phospholipids are arranged in a bilayer system,with the hydrophobic tails in close association to each other,whereas the polar heads are facing the water phase on both sides of the membrane. Associated to the phospholipid bilayer are the protein molecules which are to be classified in peripheral and integral ones. The type of interaction of the two classes of proteins with phospholipids are totally different. In the former case protein are bound to the surface via polar groups. Changes in ionic strength and/or chelation of divalent cations is often sufficient to cause the peripheral proteins to be released. On the contrary,integral proteins are firmly bound to the lipid bilayer and hydrophobic interactions contribute greatly to the stabilization of the structure. Obviously depending on the physical properties of the surface of the protein three possibilities are open: a) a protein molecule is completely embedded in the lipid bilayer; b) a protein molecule is only partially embedded in hydrophobic core of the membrane and faces one of the two surfaces with a hydrophilic tail and c) a protein molecule may be so arranged that only the intermediate portion of it shows a hydrophobic outer surface and the protein may be visualized as a transmembrane component.

Sandri G

Papers

Some properties of an isolated glycoprotein possibly related to calcium transport in mitochondria.

Intramitochondrial location of the calcium binding glycoprotein.

Intramitochondrial localization of arginase appearing in chicken liver upon starvation.