Gloria Brea-Calvo

Bio: Gloria Brea-Calvo is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Coenzyme Q – cytochrome c reductase & Mitochondrial respiratory chain. The author has an hindex of 17, co-authored 30 publications receiving 909 citations. Previous affiliations of Gloria Brea-Calvo include Carlos III Health Institute & Pablo de Olavide University.

Clinical syndromes associated with Coenzyme Q10 deficiency

Abstract: Primary Coenzyme Q deficiencies represent a group of rare conditions caused by mutations in one of the genes required in its biosynthetic pathway at the enzymatic or regulatory level. The associated clinical manifestations are highly heterogeneous and mainly affect central and peripheral nervous system, kidney, skeletal muscle and heart. Genotype-phenotype correlations are difficult to establish, mainly because of the reduced number of patients and the large variety of symptoms. In addition, mutations in the same COQ gene can cause different clinical pictures. Here, we present an updated and comprehensive review of the clinical manifestations associated with each of the pathogenic variants causing primary CoQ deficiencies.

COQ4 Mutations Cause a Broad Spectrum of Mitochondrial Disorders Associated with CoQ10 Deficiency

Abstract: Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ10 biosynthesis. CoQ10 is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations in COQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ10 biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ10 and often displayed a decrease in CoQ10-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency.

Supercomplex Assembly Determines Electron Flux in the Mitochondrial Electron Transport Chain

Abstract: The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respirasome (complexes I, III, and IV), complexes I and III, and complexes III and IV. The role of SCs is unclear, and their existence is debated. By genetic modulation of interactions between complexes I and III and III and IV, we show that these associations define dedicated CoQ and cyt c pools and that SC assembly is dynamic and organizes electron flux to optimize the use of available substrates.

Biphasic dose response in low level light therapy – an update

Abstract: Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.

Leigh Syndrome with Nephropathy and CoQ10 Deficiency Due to decaprenyl diphosphate synthase subunit 2 (PDSS2) Mutations

Abstract: Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy. Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ(10) biosynthetic pathway. Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency.

Update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA 13: suitability of taxonomic units notified to EFSA until September 2020.

Abstract: Qualified presumption of safety (QPS) was developed to provide a generic safety evaluation for biological agents to support EFSA's Scientific Panels. The taxonomic identity, body of knowledge, safety concerns and antimicrobial resistance are assessed. Safety concerns identified for a taxonomic unit (TU) are where possible to be confirmed at strain or product level, reflected by 'qualifications'. No new information was found that would change the previously recommended QPS TUs and their qualifications. The list of microorganisms notified to EFSA was updated with 54 biological agents, received between April and September 2019; 23 already had QPS status, 14 were excluded from the QPS exercise (7 filamentous fungi, 6 Escherichia coli, Sphingomonas paucimobilis which was already evaluated). Seventeen, corresponding to 16 TUs, were evaluated for possible QPS status, fourteen of these for the first time, and Protaminobacter rubrum, evaluated previously, was excluded because it is not a valid species. Eight TUs are recommended for QPS status. Lactobacillus parafarraginis and Zygosaccharomyces rouxii are recommended to be included in the QPS list. Parageobacillus thermoglucosidasius and Paenibacillus illinoisensis can be recommended for the QPS list with the qualification 'for production purposes only' and absence of toxigenic potential. Bacillus velezensis can be recommended for the QPS list with the qualification 'absence of toxigenic potential and the absence of aminoglycoside production ability'. Cupriavidus necator, Aurantiochytrium limacinum and Tetraselmis chuii can be recommended for the QPS list with the qualification 'production purposes only'. Pantoea ananatis is not recommended for the QPS list due to lack of body of knowledge in relation to its pathogenicity potential for plants. Corynebacterium stationis, Hamamotoa singularis, Rhodococcus aetherivorans and Rhodococcus ruber cannot be recommended for the QPS list due to lack of body of knowledge. Kodamaea ohmeri cannot be recommended for the QPS list due to safety concerns.

Terpenes: substances useful in human healthcare.

Abstract: Terpenes are naturally occurring substances produced by a wide variety of plants and animals. A broad range of the biological properties of terpenoids is described, including cancer chemopreventive effects, antimicrobial, antifungal, antiviral, antihyperglycemic, anti-inflammatory, and antiparasitic activities. Terpenes are also presented as skin penetration enhancers and agents involved in the prevention and therapy of several inflammatory diseases. Moreover, a potential mechanism of their action against pathogens and their influence on skin permeability are discussed. The major conclusion is that larger-scale use of terpenoids in modern medicine should be taken into consideration.