14 research outputs found
El metamorfismo hercínico de la Sierra de la Demanda (Provincias de Logroño y Burgos).
Se estudian los principales rasgos del metamorfismo hercínico de los materiales paleozoicos de la Sierra de la Demanda, en base a la caracterización de minerales arcillosos y micáceos. Asimismo, se considera su posible relación con otras áreas cercanas, con caracteres geológicos similares
Regulation of mother-to-offspring transmission of mtDNA heteroplasmy
mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission
A Mitochondria-Specific Isoform of FASTK Is Present In Mitochondrial RNA Granules and Regulates Gene Expression and Function
The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo. FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. These data provide insights into the mechanism and control of mitochondrial RNA processing within mitochondrial RNA granules
Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool
Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the
supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the
physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full
knockout for SCAF1, or the wild-type version of the protein and found that exercise performance is SCAF1 dependent.
By combining quantitative data–independent proteomics, 2D Blue native gel electrophoresis, and functional
analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV
within the N-respirasome, increases NADH-dependent respiration, and reduces reactive oxygen species (ROS).
Furthermore, the expression of AOX in cells and mice confirms that CI-CIII superassembly segments the CoQ in
two pools and modulates CI-NADH oxidative capacityMINECO
SAF2015-65633-RMCIU
RTI2018-099357-B-I00CIBERFES
CB16/10/00282Human Frontier Science Program
RGP0016/2018ISCIII-SGEFI/FEDER, ProteoRed
ISCIII-IPT13/0001Fundacio MaratoTV3
122/C/2015La Caixa Foundation
HR17-00247Ministry of Economy, Industry and Competitiveness (MEIC)Pro-CNIC FoundationMINECO award
SEV-2015-0505
MINECO-BIO2015-67580-P
PGC2018-097019-B-I0
The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency
Electrons feed into the mitochondrial electron transport chain (mETC) from NAD-or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To prevent this, the mETC superstructure can be reconfigured through the degradation of respiratory complex I, liberating associated complex III to increase electron flux via FAD at the expense of NAD. Here, we demonstrate that this adaptation is driven by the ratio of reduced to oxidized CoQ. Saturation of CoQ oxidation capacity induces reverse electron transport from reduced CoQ to complex I, and the resulting local generation of superoxide oxidizes specific complex I proteins, triggering their degradation and the disintegration of the complex. Thus, CoQ redox status acts as a metabolic sensor that fine-tunes mETC configuration in order to match the prevailing substrate profile
The current coenzyme Q science and knowledge
Coenzyme Q (CoQ) is a redox lipid essential for aerobic respiration and antioxidant protection. It is synthesized in each cell by a multiprotein complex inside mitochondria and incorporated in all cellular membranes. It is however an amazing molecule whose homeostasis not only depends on the proper function of biosynthesis complex but also on age, diet and the wholeness of mitochondria functions
Glucose metabolism links astroglial mitochondria to cannabinoid effects
Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses <sup>1-5</sup> . By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors <sup>5-7</sup> . However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB <sub>1</sub> ) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB <sub>1</sub> receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB <sub>1</sub> receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice