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At least 793 records · Page 44Linked to original sources
PubMed2005

Mitochondrial localization of CNP2 is regulated by phosphorylation of the N-terminal targeting signal by PKC: implications of a mitochondrial function for CNP2 in glial and non-glial cells.

Both 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) isoforms are abundantly expressed in myelinating cells. CNP2 differs from CNP1 by a 20 amino acid N-terminal extension and is also expressed at much lower levels in non-myelinating tissues. The functional role of CNP2, apart from CNP1, and the significance for CNP2 expression in non-myelinating tissues are unknown. Here, we demonstrate that CNP2 is translocated to mitochondria by virtue of a mitochondrial targeting signal at the N-terminus. PKC-mediated phosphorylation of the targeting signal inhibits CNP2 translocation to mitochondria, thus retaining it in the cytoplasm. CNP2 is imported into mitochondria and the targeting signal cleaved, yielding a mature, truncated form similar in size to CNP1. CNP2 is entirely processed in adult liver and embryonic brain, indicating that it is localized specifically to mitochondria in non-myelinating cells. Our results point to a broader biological role for CNP2 in mitochondria that is likely to be different from its specific role in the cytoplasm, along with CNP1, during myelination.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed2003

Mitochondrial function: the heart of myocardial preservation.

Over the past several decades, it has become widely recognized that the mitochondria serve an important role in energy production and transfer to myocardial cells. More recently, mitochondria have been shown to play a key role in cell-death pathways by activating mitochondrial permeability transition pore formation and causing the release of several proteins, such as cytochrome c and proapoptotic factors. Although the molecular mechanisms for this process are still under investigation, important mitochondrial adaptations have been identified that can inhibit permeability transition activation and prevent apoptosis and necrosis. Specifically, myocardial preconditioning is an intriguing adaptation by which brief ischemia and reperfusion prime the mitochondria so that a subsequent prolonged period of ischemia is better tolerated. Mitochondrial ATP-dependent potassium channels seem to play a critical role in triggering or mediating this protection. The objective of this review is to outline the role of the mitochondria in supporting myocardial energy under normal and ischemic conditions. It will also provide insight into the mechanisms by which mitochondrial signaling in preconditioning can protect the myocyte during subsequent prolonged ischemic periods.

Animals↗
PubMed1990

Maturation of fetal rat islet cells in vitro during tissue culture is associated with increased mitochondrial function.

Tissue culture for one or seven days of pancreatic islets isolated from 21-day old fetal rats was found to be associated with a marked increase in the oxidation of L-(U-14C) glutamine by intact islets and in the activity of both alanine-glutamate and aspartate-glutamate transaminases as well as glutamate dehydrogenase in islet homogenates. This coincided with an increase in the relative amount of mitochondrial DNA. The activities of glucose-phosphorylating enzymes (hexokinase and glucokinase), glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase were less markedly increased during the culture period than those of enzymes involved in amino acid catabolism and located, in part at least, in mitochondria. The combined data suggest that the functional maturation of fetal islets during the culture period is associated with and may be attributable to a preferential maturation of their mitochondria.

Alanine Transaminase↗
PubMed1976

Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma.

Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.

Animals↗
PubMed2005

Mitochondrial functioning of constitutive iron uptake mutations in Cryptococcus neoformans.

Randomly obtained, constitutive plasma membrane ferric reductase/ferrous uptake mutants of Cryptococcus neoformans were mapped to four distinct loci by meiotic analysis. One of those loci, FRR1 , was previously found homologous to MRS3 and MRS4 of Saccharomyces cerevisiae , which determine proteins involved in mitochondrial transport of iron. We were able to complement, clone, sequence and thereby identify two of the three remaining constitutive uptake loci. FRR3 was found to be homologous to ISU1 and ISU2 of S. cerevisiae, which form mitochondrial iron-sulfur complexes; FRR4 was found to be homologous to YFH1, the yeast frataxin homologue, which also participates in iron-sulfur cluster biogenesis. Because of the constitutive iron uptake seen in these mutants, mitochondria appear to have a central role in the cellular iron economy; moreover, as judged by our mutational statistics, the genetic machinery for mitochondrial iron accumulation may be more complex than that of the cytoplasm.

Amino Acid Sequence↗
PubMed2003

A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells.

Mitochondria are the powerhouse of the cell and their disruption leads to cell death. We have used a peptide trivalent arsenical, 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO), to inactivate the adenine nucleotide translocator (ANT) that exchanges matrix ATP for cytosolic ADP across the inner mitochondrial membrane and is the key component of the mitochondrial permeability transition pore (MPTP). GSAO triggered Ca(2+)-dependent MPTP opening by crosslinking Cys(160) and Cys(257) of ANT. GSAO treatment caused a concentration-dependent increase in superoxide levels, ATP depletion, mitochondrial depolarization, and apoptosis in proliferating, but not growth-quiescent, endothelial cells. Endothelial cell proliferation drives new blood vessel formation, or angiogenesis. GSAO inhibited angiogenesis in the chick chorioallantoic membrane and in solid tumors in mice. Consequently, GSAO inhibited tumor growth in mice with no apparent toxicity at efficacious doses.

Adenine Nucleotide Translocator 1↗
PubMed1995

Laser-excited fluorescence studies of mitochondrial function in saponin-skinned skeletal muscle fibers of patients with chronic progressive external ophthalmoplegia.

The functional behavior of mitochondria in skeletal muscle of patients with chronic progressive external ophthalmoplegia was studied by laser-excited fluorescence measurements of NAD(P)H and flavoproteins in saponin-skinned fibers. Variations in the mitochondrial content and the presence of partially respiratory chain-inhibited mitochondria can be detected using this novel method.

DNA, Mitochondrial↗
PubMed2005

Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer.

Human prostate secretory epithelial cells have the uniquely specialized function of accumulating and secreting extremely high levels of citrate. This is achieved by their ability to accumulate high cellular levels of zinc that inhibit citrate oxidation. This process of net citrate production requires unique metabolic/bioenergetic mitochondrial relationships. In prostate cancer, the malignant cells undergo a metabolic transformation from zinc-accumulating citrate-producing sane cells to citrate-oxidizing malignant cells that lost the ability to accumulate zinc. This review describes the metabolic/bioenergetic, zinc and mitochondrial relationships involved in normal and malignant prostate. Hopefully, this report will generate much needed interest and research in this neglected, but critically important, area of investigation.

Aconitate Hydratase↗
PubMed2004

Advantages in the use of carvedilol versus propranolol for the protection of cardiac mitochondrial function.

BACKGROUND: Carvedilol is a neurohormonal antagonist of multiple action which is used in clinical practice for the treatment of congestive heart failure, mild to moderate hypertension and myocardial infarction. Previous results from our group have demonstrated that one of the main targets for the protective effect of carvedilol is the cardiac mitochondrial network. In-this work, we compare the effect of carvedilol with propranolol in different models of mitochondrial dysfunction and in the generation of transmembrane electric potential (EP). We further tested if carvedilol was able to inhibit the mitochondrial permeability transition (MPT) induced by doxorubicin and calcium-dependent cytochrome c release, a phenomenon frequently associated with apoptotic cell death. METHODS: Cardiac mitochondria were isolated by differential centrifugation. Oxygen consumption and mitochondrial EP were determined using an oxygen electrode and a tetraphenylphosphonium-sensitive electrode, respectively. Changes in mitochondrial volume and the release of cytochrome c were measured with spectrophotometric techniques. RESULTS: Propranolol, compared with carvedilol, had only a marginal effect, not only in protection against MPT induction, but also against oxygen consumption linked to the oxidation of external NADH, a process that is considered by several authors as key in the cardiotoxicity of doxorubicin. Regarding EP generation, propranolol had no effect, in contrast to carvedilol, which was confirmed to act as a protonophore. For the first time we also show that carvedilol inhibits the MPT induced by doxorubicin and calcium-dependent cytochrome c release. CONCLUSIONS: With this work, we further support the notion that carvedilol is effective in several models of mitochondrial dysfunction, particularly those involving oxidative stress. The results demonstrate that for some pathological conditions, carvedilol and propranolol have different mechanisms of action at the sub-cellular level, as propranolol seems to lack effectiveness in the protection of cardiac mitochondria.

Animals↗
PubMed1996

Effects of the novel thyroid hormone analogues, SKF L-94901, DIBIT, and 3'-AC-T2 on mitochondrial function.

The effects of L-T3 (3,3',5-triiodo-L-thyronine) and three novel analogues, SKF L-94901 (3,5-Dibromo-3'-pyridazinone-L-thyronine), Dibit (3,5-Dibromo-3'-isopropyl-L-thyronine), and 3'-Ac-T2(3'-Acetyl-3,5,-Diiodo-L-thyronine), on mitochondrial parameters were determined in hypothyroid rats. The parameters include the 24 hour hormone-induced changes in the bc1 complex and in the proton permeability of the mitochondrial inner membrane. The cardiac sparing analogue, SKF L-94901, had no effect on mitochondrial respiration or proton permeability; but the analogue did increase a-glycerophosphate dehydrogenase activity, mitochondrial ubiquinone content, and altered the bypass respiration in the bc1 complex. Dibit also did not increase respiration significantly but did change the other parameters. 3'-Ac-T2 increased respiration, mitochondrial ubiquinone content, proton permeability, enzyme activity and altered the bypass of the Antimycin A blockage in the bc1 complex.

Animals↗
PubMed1993

Use of carboxyatractylate and tight-binding inhibitor theory to determine the concentration of functional mitochondrial adenine nucleotide translocators in a reconstituted system.

The adenine nucleotide translocator (AdNT) has been isolated from rat heart mitochondria and reconstituted into liposomes containing ATP. Translocator activity was determined using a coupled enzyme system to measure the ADP-induced efflux of ATP from the liposomes. In order to determine specific activity, the number of functional translocators must also be known. Carboxyatractylate (CAT) is a highly selective inhibitor of the AdNT, with Ki < 10 nM, a value sufficiently low relative to the concentration of protein in transport assays to suggest the use of tight-binding inhibitor theory to quantify functional translocators. Ackermann-Potter plots of velocity vs proteoliposome concentration at several different CAT concentrations were used both to demonstrate the occurrence of tight-binding inhibition and to determine the concentration of AdNT catalytic sites in the native orientation. The results obtained agreed well with earlier reports based on [14C]CAT binding; functionally reconstituted AdNT represented 5-10% of the protein added to the system. Specific activities were ca. 7-10 mumol/min mg depending on the lipid composition of the liposomes. Unincorporated protein did not appreciably affect the measurements. This methodology should be readily applicable to any reconstituted systems for which high-affinity inhibitors which bind only to active protein are known.

Animals↗
PubMed1986

[Assessment of mitochondrial function in the surviving cytoplasts of cultured cells of pig embryonic kidney by using ethylrhodamine].

A study was made of the functional state of chondriome in cytoplasts previously cultivated for a long time under vital staining with fluorescent dye ethylrhodamine (10 micrograms/ml) which is known to accumulate preferentially in mitochondria. The energization was estimated by the intensity of mitochondrial fluorescence. It was realized that 30 minutes after enucleation cytoplasts retained the same fluorescence as did the untreated cells, and that the mitochondrial distribution within the cell was very similar. Such a high intensity of fluorescence seen within one day after enucleation gives a strong evidence on the high degree of independence on the cell nucleus of organelles that provide the energy to metabolic processes. In the course of survival in the cultivation medium for 1-4 days the intensity of fluorescence is shown to fall, especially on the second day after enucleation. All these changes coincide with the changes in cytoplast shape: originally well spread bodies transform into squeezed, ball-shaped or strongly deformed ones. The adhesive ability is going down, and in result only single units of cytoplast can hardly be found on the cover slips by the 4th day after enucleation. These changes give evidence on the enhanced degeneration of cultured cytoplasts.

Animals↗