Institute Biomedicina Valencia
Institute Biomedicina Valencia
Landete J.M.,CSIC - Institute of Agricultural Chemistry and Food Technology |
Garcia-Haro L.,CSIC - Institute of Agricultural Chemistry and Food Technology |
Garcia-Haro L.,Institute Biomedicina Valencia |
Blasco A.,CSIC - Institute of Agricultural Chemistry and Food Technology |
And 4 more authors.
Applied and Environmental Microbiology | Year: 2010
Lactobacillus casei can metabolize L-malic acid via malolactic enzyme (malolactic fermentation [MLF]) or malic enzyme (ME). Whereas utilization of L-malic acid via MLF does not support growth, the ME pathway enables L. casei to grow on L-malic acid. In this work, we have identified in the genomes of L. casei strains BL23 and ATCC 334 a cluster consisting of two diverging operons, maePE and maeKR, encoding a putative malate transporter (maeP), an ME (maeE), and a two-component (TC) system belonging to the citrate family (maeK and maeR). Homologous clusters were identified in Enterococcus faecalis, Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus uberis. Our results show that ME is essential for L-malic acid utilization in L. casei. Furthermore, deletion of either the gene encoding the histidine kinase or the response regulator of the TC system resulted in the loss of the ability to grow on L-malic acid, thus indicating that the cognate TC system regulates and is essential for the expression of ME. Transcriptional analyses showed that expression of maeE is induced in the presence of L-malic acid and repressed by glucose, whereas TC system expression was induced by L-malic acid and was not repressed by glucose. DNase I footprinting analysis showed that MaeR binds specifically to a set of direct repeats [5'-TTATT(A/T)AA-3'] in the mae promoter region. The location of the repeats strongly suggests that MaeR activates the expression of the diverging operons maePE and maeKR where the first one is also subjected to carbon catabolite repression. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Garcia-Gimenez J.L.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
Garcia-Gimenez J.L.,University of Valencia |
Gimeno A.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
Gimeno A.,University of Valencia |
And 11 more authors.
PLoS ONE | Year: 2011
Background: Friedreich's ataxia (FRDA) is a mitochondrial rare disease, which molecular origin is associated with defect in the expression of frataxin. The pathological consequences are degeneration of nervous system structures and cardiomyopathy with necrosis and fibrosis, among others. Principal Findings: Using FRDA fibroblasts we have characterized the oxidative stress status and mitochondrial biogenesis. We observed deficiency of MnSOD, increased ROS levels and low levels of ATP. Expression of PGC-1α and mtTFA was increased and the active form of the upstream signals p38 MAPK and AMPK in fibroblasts from two patients. Interestingly, the expression of energetic factors correlated with the natural history of disease of the patients, the age when skin biopsy was performed and the size of the GAA expanded alleles. Furthermore, idebenone inhibit mitochondriogenic responses in FRDA cells. Conclusions: The induction of mitochondrial biogenesis in FRDA may be a consequence of the mitochondrial impairment associated with disease evolution. The increase of ROS and the involvement of the oxidative phosphorylation may be an early event in the cell pathophysiology of frataxin deficiency, whereas increase of mitochondriogenic response might be a later phenomenon associated to the individual age and natural history of the disease, being more evident as the patient age increases and disease evolves. This is a possible explanation of heart disease in FRDA. © 2011 García-Giménez et al.