Intramitochondrial cholesterol transfer

Cholesterol serves as the initial substrate for all steroid hormones synthesized in the body regardless of the steroidogenic tissue or final steroid produced. The first steroid formed in the steroidogenic pathway is pregnenolone which is formed by the excision of a six carbon unit from cholesterol by the cytochrome P450 side chain cleavage enzyme system which is located in the inner mitochondrial membrane. It has long been known that the regulated biosynthesis of steroids is controlled by a cycloheximide sensitive factor whose function is to transfer cholesterol from the outer to the inner mitochondrial membrane, thus, the identity of this factor is of great importance. A candidate for the regulatory factor is the mitochondrial protein, the steroidogenic acute regulatory (StAR) protein. Cloning and sequencing of the StAR cDNA indicated that it was a novel protein, and transient transfections with the cDNA for the StAR protein resulted in increased steroid production in the absence of stimulation. Mutations in the StAR gene cause the potentially lethal disease congenital lipoid adrenal hyperplasia, a condition in which cholesterol transfer to the cytochrome P450 side chain cleavage enzyme, P450scc, is blocked, filling the cell with cholesterol and cholesterol esters. StAR knockout mice have a phenotype which is essentially identical to the human condition. The cholesterol transferring activity of StAR has been shown to reside in the C-terminal part of the molecule and a protein sharing homology with a region in the C-terminus of StAR has been shown to display cholesterol transferring capacity. Recent evidence has indicated that StAR can act as a sterol transfer protein and it is perhaps this characteristic which allows it to mobilize cholesterol to the inner mitochondrial membrane. However, while it appears that StAR is the acute regulator of steroid biosynthesis via its cholesterol transferring activity, its mechanism of action remains unknown.     

Intramitochondrial phospholipid trafficking

Mitochondrial functions and architecture rely on a defined lipid composition of their outer and inner membranes, which are characterized by a high content of non-bilayer phospholipids such as cardiolipin (CL) and phosphatidylethanolamine (PE). Mitochondrial membrane lipids are synthesized in the endoplasmic reticulum (ER) or within mitochondria from ER-derived precursor lipids, are asymmetrically distributed within mitochondria and can relocate in response to cellular stress. Maintenance of lipid homeostasis thus requires multiple lipid transport processes to be orchestrated within mitochondria. Recent findings identified members of the Ups/PRELI family as specific lipid transfer proteins in mitochondria that shuttle phospholipids between mitochondrial membranes. They cooperate with membrane organizing proteins that preserve the spatial organization of mitochondrial membranes and the formation of membrane contact sites, unravelling an intimate crosstalk of membrane lipid transport and homeostasis with the structural organization of mitochondria.This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.     

Effect of magnesium supplementation and training on magnesium tissue distribution in rats

The aim of this work is to study the effect of training and Mg supplementation on body pools of Mg and on Mg tissue distribution. Forty male Wistar rats were divided into four groups (n=10): control group (C); trained group (T); Mg-supplemented group (+Mg); and trained and Mg-supplemented group (+MgT). The Mg supplement (100 ppm of Mg) was given in the drinking water for 21 d. The training consisted of swimming during 60% of maximal swimming time obtained in the first session to exhaustion, during 3 wk (5 d a week). The variables measured were: erythrocytes (RBC), hemoglobin (Hb), hematocrit (Hto), total proteins (TP), and Mg in serum, RBC, liver, muscle, bone, and kidney. There was less Mg in liver, muscle, and erythrocyte in trained animals than in control or supplemented animals (T vs C, +MgT vs C and +MgT vs +Mg) (p < 0.01). Trained antimals (T and +MgT) showed higher Mg kidney rates than the untrained ones (p<0.01). There was less bone Mg in control (C) and in supplemented and trained (+MgT) groups than in trained (T) and in supplemented (+Mg) animals (p<0.01). Serum Mg showed a decreasing concentration profile in the following order: +Mg, +MgT, T, C (p<0.01). We conclude that Mg supplementation improves bone and serum Mg levels, but this does not affect Mg status in soft tissues. Maintained exercise leads to a diminution of Mg in the aforementioned soft tissues that is not noticeable in serum, probably provoked by an increase of renal excretion.     

Intramitochondrial bodies in bovine adrenocortical cells

Summary Electron dense, homogeneous, mostly round intramitochondrial bodies were found in bovine adrenal glands, predominantly in the zona glomerulosa. The histochemical results obtained suggest that these bodies might contain a considerable amount of protein, although the possibility that substances other than proteins are contained in these bodies cannot be completely ruled out. The physiological significance of the intramitochondrial bodies remains unclear.This work was supported by a Scientific Research Grant, No. 144017, from the Ministry of Education of Japan to Prof. M. YasudaThe authors are deeply indebted to Dr. Kazuyori Yamada, Department of Anatomy, Nagoya University for his generosity in allowing us to perform a part of the histochemical tests in his laboratory and for the use of the facilities     

Intramitochondrial proteolytic activity of rat liver]

Highly purified mitochondria and lysosomes are isolated from rat liver homogenate. pH optimum of proteolytic activity with respect to proteins of own structures and to mitochondrial structural protein is investigated. The purification of mitochondria from lysosomes is found to be accompanied by the change of proteolytic activity pH optimum from 5.0 to 6.0 in coarse and purified mitochondria respectively. Comparative study of structural protein hydrolysis products with enzyme preparations from purified mitochondria and lysosomes has revealed differences in the spectrum of the reaction products. The data obtained suggest a presence of a proteolytic enzyme in rat liver mitochondria.     

Intramitochondrial rodlet-like inclusions in human leukemic lymphocytes.

Some mitochondria in leukemic cells in two of nine investigated patients with chronic lymphocytic leukemia and in one patient with morphologically less usual form of this disease contained unusual rodlet-like inclusion bodies. These structures were always present in the matrix of frequently dilatated intercristal spaces. The width of rodlet-like inclusions ranged between 10 and 20 nm, their maximal length was 114 nm. All observed rodlet-like inclusion bodies appeared to be composed of fine filaments 2...3 nm in width and resembled the DNA containing structures in mitochondria of few other cell types. In mitochondria of leukemic cells, however, these inclusions represent a further structural abnormality.