Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

Abstract: Originally identified as a key component of the mitochondrial respiratory chain, Co enzyme Q (CoQ or CoQ10 for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane types. Cells rely on endogenous CoQ biosynthesis, and defects in this still-not completely understood pathway result in primary CoQ deficiencies, a group of conditions biochemically characterised by decreased tissue CoQ levels, which in turn are linked to functional defects. Secondary CoQ deficiencies may result from a wide variety of cellular dysfunctions not directly linked to primary synthesis. In this article, we review the current knowledge on CoQ biosynthesis, the defects leading to diminished CoQ10 levels in human tissues and their associated clinical manifestations

Cell Survival from Chemotherapy Depends on NF-κB Transcriptional Up-Regulation of Coenzyme Q Biosynthesis

9 pages and 6 figures.[Background] Coenzyme Q (CoQ) is a lipophilic antioxidant that is synthesized by a mitochondrial complex integrated by at least ten nuclear encoded COQ gene products. CoQ increases cell survival under different stress conditions, including mitochondrial DNA (mtDNA) depletion and treatment with cancer drugs such as camptothecin (CPT). We have previously demonstrated that CPT induces CoQ biosynthesis in mammal cells.[Methodology/Principal Findings] CPT activates NF-κB that binds specifically to two κB binding sites present in the 5′-flanking region of the COQ7 gene. This binding is functional and induces both the COQ7 expression and CoQ biosynthesis. The inhibition of NF-κB activation increases cell death and decreases both, CoQ levels and COQ7 expression induced by CPT. In addition, using a cell line expressing very low of NF-κB, we demonstrate that CPT was incapable of enhancing enhance both CoQ biosynthesis and COQ7 expression in these cells.[Conclusions/Significance] We demonstrate here, for the first time, that a transcriptional mechanism mediated by NF-κB regulates CoQ biosynthesis. This finding contributes new data for the understanding of the regulation of the CoQ biosynthesis pathway.This work was supported by spanish Ministerio de Educacion y Ciencia Grant BFU2005-03017.Peer reviewe

Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy

Constitutive expression of the chemokine Mcp1 in mouse cardiomyocytes creates a model of inflammatory cardiomyopathy, with death from heart failure at age 7-8 months. A critical pathogenic role has previously been proposed for induced oxidative stress, involving NADPH oxidase activation. To test this idea, we exposed the mice to elevated oxygen levels. Against expectation, this prevented, rather than accelerated, the ultrastructural and functional signs of heart failure. This result suggests that the immune signaling initiated by Mcp1 leads instead to the inhibition of cellular oxygen usage, for which mitochondrial respiration is an obvious target. To address this hypothesis, we combined the Mcp1 model with xenotopic expression of the alternative oxidase (AOX), which provides a sink for electrons blocked from passage to oxygen via respiratory complexes III and IV. Ubiquitous AOX expression provided only a minor delay to cardiac functional deterioration and did not prevent the induction of markers of cardiac and metabolic remodeling considered a hallmark of the model. Moreover, cardiomyocyte-specific AOX expression resulted in exacerbation of Mcp1-induced heart failure, and failed to rescue a second cardiomyopathy model directly involving loss of cIV. Our findings imply that mitochondria! involvement in the pathology of inflammatory cardiomyopathy is multifaceted and complex.Peer reviewe

Cellular Robustness Conferred by Genetic Crosstalk Underlies Resistance against Chemotherapeutic Drug Doxorubicin in Fission Yeast

10.1371/journal.pone.0055041PLoS ONE81

Measurement of CP -violating and mixing-induced observables in Bs0→ϕγ decays

A time-dependent analysis of the B 0 s → ϕ γ decay rate is performed to determine the C P -violating observables S ϕ γ and C ϕ γ and the mixing-induced observable A Δ ϕ γ . The measurement is based on a sample of p p collision data recorded with the LHCb detector, corresponding to an integrated luminosity of 3     fb − 1 at center-of-mass energies of 7 and 8 TeV. The measured values are S ϕ γ = 0.43 ± 0.30 ± 0.11 , C ϕ γ = 0.11 ± 0.29 ± 0.11 , and A Δ ϕ γ = − 0.67 + 0.37 − 0.41 ± 0.17 , where the first uncertainty is statistical and the second systematic. This is the first measurement of the observables S and C in radiative B 0 s decays. The results are consistent with the standard model predictions

Observation of the Λb0 → χc1 (3872) pK− decay

No abstract available

Observation of a narrow pentaquark state, P-c(4312)(+), and of the two-peak structure of the P-c(4450)(+)

A narrow pentaquark state, P-c(4312)(+), decaying to J/psi p, is discovered with a statistical significance of 7.3 sigma in a data sample of Lambda(0)(b) -> J/psi pK(-) decays, which is an order of magnitude larger than that previously analyzed by the LHCb Collaboration. The P-c(4450)(+) pentaquark structure formerly reported by LHCb is confirmed and observed to consist of two narrow overlapping peaks, P-c(4440)(+) and P-c(4457)(+), where the statistical significance of this two-peak interpretation is 5.4 sigma. The proximity of the Sigma(+)(c)(D) over bar (0) and Sigma(+)(c)(D) over bar (*0) thresholds to the observed narrow peaks suggests that they play an important role in the dynamics of these states