[The underestimated coding potential of mitochondrial DNA]. / L'ADN mitochondrial, un potentiel codant mésestimé.

Mitochondria are ancient organelles that emerged from the endosymbiosis of free-living proto-bacteria. They still retain a semi-autonomous genetic system with a small genome. Mitochondrial DNA (mtDNA) codes for 13 essential proteins for the production of ATP, the sequences of which are relatively conserved across Metazoans. The discovery of additional mitochondria-derived peptides (MDPs) indicates an underestimated coding potential. Humanin, an anti-apoptotic peptide, is likely independently transcribed from within the 16S rRNA gene, as are recently described SHLPs. MOTS-c, discovered in silico, has been demonstrated to be involved in metabolism and insulin sensitivity. Gau, is a positionally conserved open reading frame (ORF) sequence found in the antisense strand of the COX1 gene and its corresponding peptide is strictly colocalized with mitochondrial markers. In bivalves with doubly uniparental inheritance of mtDNA, male and female mtDNAs each carry a separate additional gene possibly involved in sex determination. Other MDPs likely exist and their investigation will shed light on the underestimated functional repertoire of mitochondria.

Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline.

Carriers of an epsilon 4 allele (E4) of apolipoprotein E (APOE) develop Alzheimer's disease (AD) earlier than carriers of other APOE alleles. The metabolism of plasma docosahexaenoic acid (DHA, 22:6n-3), an omega-3 fatty acid (n-3 FA), taken up by the brain and concentrated in neurons, is disrupted in E4 carriers, resulting in lower levels of brain DHA. Behavioural and cognitive impairments have been observed in animals with lower brain DHA levels, with emphasis on loss of spatial memory and increased anxiety. E4 mice provided a diet deficient in n-3 FA had a greater depletion of n-3 FA levels in organs and tissues than mice carrying other APOE alleles. However, providing n-3 FA can restore levels of brain DHA in E4 animals and in other models of n-3 FA deficiency. In E4 carriers, supplementation with DHA as early as possible might help to prevent the onset of AD and could halt the progression of, and reverse some of the neurological and behavioural consequences of their higher vulnerability to n-3 FA deficiency.

Identification of members of the gonadotropin-releasing hormone (GnRH), corticotropin-releasing factor (CRF) families in the genome of the holocephalan, Callorhinchus milii (elephant shark).

The gonadotropin-releasing hormone (GnRH) and corticotropin-releasing family (CRF) are two neuropeptides families that are strongly conserved throughout evolution. Recently, the genome of the holocephalan, Callorhinchus milii (elephant shark) has been sequenced. The phylogenetic position of C. milii, along with the relatively slow evolution of the cartilaginous fish suggests that neuropeptides in this species may resemble the earliest gnathostome forms. The genome of the elephant shark was screened, in silico, using the various conserved motifs of both the vertebrate CRF paralogs and the insect diuretic hormone sequences to identify the structure of the C. milii CRF/DH-like peptides. A similar approach was taken to identify the GnRH peptides using conserved motifs in both vertebrate and invertebrate forms. Two CRF peptides, a urotensin-1 peptide and a urocortin 3 peptide were found in the genome. There was only about 50% sequence identity between the two CRF peptides suggesting an early divergence. In addition, the urocortin 2 peptide seems to have been lost and was identified as a pseudogene in C. milii. In contrast to the number of CRF family peptides, only a GnRH-II preprohormone with the conserved mature decapeptide was found. This confirms early studies about the identity of GnRH in the Holocephali, and suggests that the Holocephali and Elasmobranchii differ with respect to GnRH structure and function.