Gloria Brea Calvo

Gloria Brea Calvo
Universidad Pablo de Olavide | UPO · Department of Physiology, Anatomy and Cellular Biology

PhD

About

53
Publications
10,220
Reads
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1,117
Citations
Citations since 2017
20 Research Items
708 Citations
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2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
Introduction
Gloria Brea Calvo currently works at the Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide (UPO). Gloria does research in Molecular and Cell Biology of mitochondria in the Andalusian Centre of Developmental Biology (CABD), a hybrid institute from UPO, CSIC and Junta de Andalucía. She is currently working on Coenzyme Q deficiencies, particularly those caused by mutations in COQ4, one of the genes involved in Coenzyme Q biosynthesis.
Additional affiliations
January 2014 - June 2016
Universidad Pablo de Olavide
Position
  • Researcher / University teacher
September 2013 - present
Universidad Pablo de Olavide
Position
  • Professor (Assistant)
October 2010 - August 2013
MRC Mitochondrial Biology Unit
Position
  • Marie Curie Fellow

Publications

Publications (53)
Article
Full-text available
Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous trainin...
Article
Full-text available
Primary coenzyme Q10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequenci...
Chapter
Coenzyme Q (CoQ) is a lipidic molecule that transfers electrons between complexes I and II to complex III in the mitochondrial respiratory chain. It is also essential for processes mediated by other mitochondrial dehydrogenases, such as those involved in pyrimidine nucleotides biosynthesis, beta-oxidation and sulfide biosynthesis. A nuclear-encoded...
Article
Coenzyme Q10 (CoQ10 ) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mito...
Article
Primary Coenzyme Q (CoQ) deficiencies are clinically heterogeneous conditions and lack clear genotype-phenotype correlations, complicating diagnosis and prognostic assessment. Here we present a compilation of all the symptoms and patients with primary CoQ deficiency described in the literature so far and analyse the most common clinical manifestati...
Article
Full-text available
The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data allow the design of secondary analyses that take advantage of this information to create new knowledge. One of these feasible analyses is the evalu...
Preprint
Full-text available
The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data now allows the design of secondary analyses that take advantage of this information to create new knowledge through specific computational approach...
Article
Full-text available
Moderate overexpression of Opa1, the master regulator of mitochondrial cristae morphology, significantly improved mitochondrial damage induced by drugs, surgical denervation, or OXPHOS defects due to specific impairment of a single mitochondrial respiratory chain complex. Here, we investigated the effectiveness of this approach in the Mpv17-/- mous...
Preprint
Full-text available
Moderate overexpression of Opa1, encoding a master regulator of mitochondrial cristae morphology, significantly improves damage induced by drugs, surgical denervation, or genetically determined single defects of mitochondrial complex I or IV. Here, we show the effectiveness of Opa1 overexpression in the Mpv17-/- mouse, characterized by profound, mu...
Article
Full-text available
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 lev...
Preprint
Full-text available
Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain...
Article
Full-text available
Coenzyme Q (CoQ), a redox-active lipid, is comprised of a quinone group and a polyisoprenoid tail. It is an electron carrier in the mitochondrial respiratory chain, a cofactor of other mitochondrial dehydrogenases, and an essential antioxidant. CoQ requires a large set of enzymes for its biosynthesis; mutations in genes encoding these proteins caus...
Article
Background Primary CoQ deficiency occurs because of the defective biosynthesis of coenzyme Q, one of the key components of the mitochondrial electron transport chain. Patients with this disease present with a myriad of non-specific symptoms and signs, posing a diagnostic challenge. Whole-exome sequencing is vital in the diagnosis of these cases. C...
Article
Full-text available
Alternative oxidases (AOXs) bypass respiratory complexes III and IV by transferring electrons from coenzyme Q directly to O2. They have therefore been proposed as a potential therapeutic tool for mitochondrial diseases. We crossed the severely myopathic skeletal muscle-specific COX15 knockout (KO) mouse with an AOX-transgenic mouse. Surprisingly, t...
Article
Full-text available
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-p...
Article
Full-text available
Physical exercise includes different levels of intensity, duration and frequency. Resistance exercise is basically anaerobic by nature with short duration and high intensity that is aimed at increasing muscular mass and strength. Conversely, an aerobic or endurance exercise takes place for a long period, with variable intensities and low resistance...
Article
Coenzyme Q (CoQ) is a unique electron carrier in the mitochondrial respiratory chain, which is synthesized on-site by a nuclear encoded multiprotein complex. CoQ receives electrons from different redox pathways, mainly NADH and FADH2 from tricarboxylic acid pathway, dihydroorotate dehydrogenase, electron transfer flavoprotein dehydrogenase and glyc...
Article
Full-text available
Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least ten...
Article
Full-text available
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...
Article
Full-text available
MPV17 is a mitochondrial protein of unknown function, and mutations in MPV17 are associated with mitochondrial deoxyribonucleic acid (DNA) maintenance disorders. Here we investigated its most similar relative, MPV17L2, which is also annotated as a mitochondrial protein. Mitochondrial fractionation analyses demonstrate MPV17L2 is an integral inner m...
Article
Full-text available
Amino acids are essential for cell growth and proliferation for they can serve as precursors of protein synthesis, be remodelled for nucleotide and fat biosynthesis, or be burnt as fuel. Mitochondria are energy producing organelles that additionally play a central role in amino acid homeostasis. One might expect mitochondrial metabolism to be geare...
Article
Full-text available
Amino acids are essential for cell growth and proliferation for they can serve as precursors of protein synthesis, be remodelled for nucleotide and fat biosynthesis, or be burnt as fuel. Mitochondria are energy producing organelles that additionally play a central role in amino acid homeostasis. One might expect mitochondrial metabolism to be geare...
Article
Full-text available
A growing number of DNA transacting proteins is found in the nucleus and in mitochondria, including the DNA repair and replication protein Flap endonuclease 1, FEN1. Here we show a truncated FEN1 isoform is generated by alternative translation initiation, exposing a mitochondrial targeting signal. The shortened form of FEN1, which we term FENMIT, l...
Data
The truncated isoform of FEN1 corresponds in size to a product initiating translation from M65 in human cells. (A) Immunoblotting of inducible HEK293T cells after selection of clones expressing FLAG-tagged full-length FEN1 (FEN11.F) and truncated FEN1 forced to start translation from M65 (FEN165.F). Transgene expression was induced with 1 or 3 ng/m...
Data
Long and short forms of FEN1 are expressed in several human cell lines, the short form is consistent with translation initiation from an internal methionine and is predicted to be targeted to mitochondria.(A) Expression of full-length FEN1 and a shorter protein (FEN1S) were detected by a FEN1 antibody in trypsin-treated human mitochondria of osteos...
Data
Model of FENMIT binding to mitochondrial DNA at the origin of replication. The mitochondrial RNA Polymerase (mtRNAP) transcribes an RNA (red line) molecule from the light strand promoter (LSP) that can serve as a primer for H-strand DNA (blue line) synthesis by DNA polymerase γ (POLG). The RNA primer must minimally be in the form of an RNA/DNA hybr...
Data
This file includes supplementary materials and methods and the in silico predicted DNA and RNA binding properties of FEN1 and FENMIT. (DOCX)
Data
Endonuclease and nucleic acid binding properties of recombinant human FEN1 variants. Recombinant FEN1 variants (1 and 5 nM) and 0.2 nM of radiolabeled (A) equilibrating 19 nt 5′ ssDNA flap substrate (T1:U1:19DNA*). FEN1 cleavage was assessed by non-denaturing 10% PAGE, with the cleavage products formed by FEN1.His in panel C arbitrarily set as 100%...
Data
The majority of FENMIT remains free of mtDNA in the presence of oxidative stress and DNA damaging agents. (A) Cells were treated with 200 µM of H2O2 for 1 h followed by mitochondrial extraction or (B) exposed to 20 Joules/m2 of UV and then allowed to recover for 18 h prior to mitochondrial extraction. Mitochondrial lysates were centrifuged through...
Data
dATI and mitochondrial targeting occur primarily with FEN165. (A) SDS-PAGE gel of [35S]-methionine-labeled FEN1 polypeptide variants generated in vitro. “M67”, “M65”, “M37” and “M1” refer to the methionines where translation starts, all of which have an artificial consensus Kozak sequence (GCCACCAUG). “WT M1” indicates that the AUG encoding M1 is p...
Data
Immunoblotting following immunoprecipitation of FENMIT.F from mitochondria of cells treated with and without EB. Immunoblots detecting transgenic FENMIT.F, and endogenous proteins (TFAM and mtRNAP) after immunoprecipitation with Anti-Flag® M2 Affinity gel (Sigma) from purified mitochondrial lysates. Control and ethidium bromide (EB) samples were al...
Article
Full-text available
Alternative translation initiation (ATI) is a mechanism of producing multiple proteins from a single transcript, which in some cases regulates trafficking of proteins to different cellular compartments, including mitochondria. Application of a genome-wide computational screen predicts a cryptic mitochondrial targeting signal for 126 proteins in mou...
Article
Full-text available
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 demonstr...
Article
Full-text available
It has recently been shown that the microtubule cytoskeleton is reformed during the execution phase of apoptosis. We demonstrate that this microtubule reformation occurs in many cell types and under different apoptotic stimuli. We confirm that the apoptotic microtubule network possesses a novel organization, whose nucleation appears independent of...
Article
Our aim was to report a new case with cerebellar ataxia associated with coenzyme Q10 (CoQ) deficiency, the biochemical findings caused by this deficiency and the response to CoQ supplementation. A 12-year-old girl presenting ataxia and cerebellar atrophy. BIOCHEMICAL STUDIES: Coenzyme Q10 in muscle was analysed by HPLC with electrochemical detectio...
Article
Full-text available
Free radicals have been implicated in the action of many chemotherapeutic drugs. Here we tested the hypothesis that camptothecin and other chemotherapeutic drugs, such as etoposide, doxorubicin, and methotrexate, induce an increase in coenzyme Q(10) levels as part of the antioxidant defense against free radical production under these anticancer tre...
Article
Full-text available
Chemotherapy-induced apoptosis by DNA-damaging drugs is thought to be generally dependent on the release of cytochrome c and the subsequent activation of caspase-9 and -3. However, the molecular mechanism of how damaged DNA triggers the apoptotic process is not clear. To better understand the mechanisms underlying this process, we examined drug-ind...
Article
Coenzyme Q (Q) is an essential factor in the mitochondrial electron chain but also exerts important antioxidant functions in the rest of cell membranes of aerobic organisms. However, the mechanisms of distribution of Q among cell membranes are largely unclear. The aim of the present work is to study the mechanisms of distribution of endogenous Q(10...
Article
Full-text available
An accelerated activity of the GD3 synthase (ST8), with consequent GD3 accumulation, is part of the response to environmental stressors in different cell types. Depending on specific, yet largely undefined, cellular settings, this can be followed by adaptation or apoptosis, the latter mostly due to GD3-induced mitochondrial damage. Here we show tha...
Article
Full-text available
Recent observations show a positive correlation between the expression of cyclooxygenase (COX), especially COX-2), and cancer development. Here we tested the hypothesis that expression of COX-2 could influence apoptosis in lung cancer cell lines. To address this question, we determined the effects of camptothecin-induced apoptosis on three lung can...
Article
Full-text available
In this study, we show that reactive oxygen species production induced by tumour necrosis factor alpha (TNF-alpha) in L929 cells was associated with a decrease in the steady-state mRNA levels of the mitochondrial transcript ATPase 6-8. Simultaneously, the transcript levels of two nuclear-encoded glycolytic enzymes, glyceraldehyde-3-phosphate dehydr...
Article
Transcription coupled repair (TCR), a special sub-pathway of nucleotide excision repair (NER), removes transcription blocking lesions rapidly from the transcribing strand of active genes. In this study, we have evaluated the importance of the TCR pathway in the induction of chromosomal aberrations and apoptosis in isogenic Chinese hamster cell line...

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Projects (2)
Project
Are the adaptations to physical exercise age-dependent? Are the adaptations to physical exercise intensity-dependent? Can high intensity exercise provide us with the same beneficial adaptations that classic endurance training provides?