Mitochondria and aging: innocent bystanders or guilty parties?

There are many theories of aging and a number ofthem encompass the role of mitochondria in this process. Mitochondrial DNA mutations and deletions have been shown to accumulate in many tissues in mammals during aging. However, there is little evidence that these mutations could affect the functioning of aging tissues.     

The mitochondrial death squad: hardened killers or innocent bystanders?

Since the discovery that formation of the apoptosome in mammalian cells is triggered by cytochrome c released from the mitochondria, many other mitochondrial proteins have been suspected to be part of a conspiracy to cause cell death. AIF, EndoG, ANT, cyclophilin D, Bit1, p53AIP, GRIM-19, DAP3, Nur77/TR3/NGFB-1, HtrA2/Omi and Smac/Diablo have all been convicted as killers, but new genetic technology is raising questions about their guilt. Gene knockout experiments suggest that many were wrongly convicted on circumstantial evidence, and just happened to be in the wrong place at the wrong time.     

Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene lead to the formation of two fusion genes: X-RARalpha and RARalpha-X (where X is the alternative RARalpha fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X-RARalpha fusion protein is indeed oncogenic. However, recent data indicate that the RARalpha-X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.     

Peptide deformylase of eukaryotic protists: a target for new antiparasitic agents?

Peptide deformylase is found only in Eubacteria, making it a logical target for discovering new antibacterial agents. Although this protein is absent from animal or fungal cells, evidence supports its existence in eukaryotic protists, including the causative agents of malaria, sleeping sickness, Chagas disease and leishmaniosis. Here, Thierry Meinnel discusses the idea that deformylase inhibitors could be used as very broad-spectrum antibiotics against bacterial infections, as well as parasitic diseases.     

Cortisol and testosterone: Inhibitory agents of the mineralocorticoid pathway. Is there a physiopathological meaning in adrenal tumors?

The authors incubated adrenal mitochondria to study the in vitro action of cortisol and testosterone on the transformation of corticosterone and 18-hydroxycorticosterone into aldosterone. The results show that cortisol at concentrations of 5 × 10⁻⁶ and 10⁻⁴ M inhibit the conversion of corticosterone into aldosterone by 23.6 to 90%; testosterone 5 × 10⁻⁵ and 10⁻⁴ M inhibit the reaction by 78.4 and 87.2%, respectively. The inhibition of the conversion of 18-hydroxycorticosterone into aldosterone is 12.5 to 91% by cortisol with concentrations ranging from 5 × 10⁻⁷ to 5 × 10⁻⁵ M and testosterone 5 × 10⁻⁵ and 10⁻⁴ M inhibits the reaction by 87.3 and 91%, respectively. Aldosterone (10⁻⁸ and 10⁻⁶ M) does not inhibit aldosterone biosynthesis from corticosterone or 18-hydroxycorticosterone. It thus appears that cortisol and testosterone have an effect on the aldosterone biosynthesis pathways in mitochondria. This action may be located at the binding site of the cytochrome P450 11β, which catalyzes all hydroxylation steps in the mineralocorticoid biosynthesis pathway. Because cortisol and testosterone may interfere with aldosterone biosynthesis, and since functional zonation is expected in adrenal carcinomas, the presence of these steroids in substantial amounts could explain the very low plasma aldosterone level usually observed, in adrenal carcinomas studies in our laboratory.     

Radwaste at sea: A new era of polarization or a new basis for consensus?

Abstract

A coalition of third world nations, led by the Pacific island countries and those European nations who have developed land‐based disposal programs for their radioactive wastes, seek to amend the London Convention on Dumping (the international treaty controlling ocean disposal of radioactive and other wastes) in order to ban ocean disposal of low‐level radioactive wastes. Pro‐dumping nations maintain that the treaty may only be amended based on science and that current scientific research indicates that low‐level waste represents neither a threat to the integrity of the marine environment nor human health. Anti‐dumping nations, on the other hand, argue that the same science, particularly the models used to predict the fate and the effects of these wastes, exhibits sufficient uncertainty to preclude judgments about the absence of harm from future disposal activities. These differing conclusions mirror differing assessments of risk. These assessments build on the differing social, political, and economic values placed on use of the ocean and on conflicting conceptions of the fundamental rights and obligations of nations whose use of the ocean may impinge on the resources of others. Each side's continued intransigence may result in unilateral ocean disposal activities with serious consequences for the London Convention on Dumping (LDC) and its control over other wastes transported to sea for disposal. Initiatives of anti‐dumping nations to expand the LDC's decision‐making framework to examine the social, economic, and political issues underlying each side's interpretation of scientific evidence offer hope to address the underlying non‐scientific issues and perhaps to strengthen decision‐making within the LDC.     

Peptostreptococcus vaginalis or Peptostreptococcus prevotii? Identification and clinical importance of a new species of Peptostreptococcus

Peptostreptococcus vaginalis is a recently described species of Gram-positive anaerobic coccus. We report one case in which P. vaginalis was isolated in pure culture from an abscess on the upper arm, and summarise nine further cases where it was isolated in mixed culture from other superficial sites, particularly infected leg ulcers. We suggest that clinical strains of P. vaginalis have probably been described in the past as Peptostreptococcus prevotii, a species which has frequently been reported from clinical surveys of anaerobic infections; their relative importance and appropriate treatment are discussed. Preformed enzyme profiles provide a simple method of identification accessible to routine diagnostic laboratories; when clinically significant isolates of GPAC are isolated in pure growth, they should be identified to the species level by use of preformed enzyme kits.     

Chemokines: a new class of neuromodulator?

Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood-brain barrier, open a new era of research in neuroscience.