Araceli del Arco

Araceli del Arco
University of Castilla-La Mancha · Faculty of Environmental Sciences and Biochemistry of Toledo

About

96
Publications
7,818
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,150
Citations
Citations since 2017
14 Research Items
1241 Citations
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
Introduction
Skills and Expertise
Additional affiliations
January 1996 - April 2016
University of Castilla-La Mancha
Position
  • Professor (Associate)

Publications

Publications (96)
Article
Introduction: The regulation of adenine nucleotide levels in the mitochondria and the cytosol is essential for cell metabolism. To sustain mitochondrial respiration, ATP generated by ATP synthase must be exported to the cytosol, whereas mitochondria must be refilled with ADP and Pi. Adenine Nucleotide Translocases (ANTs), which catalyze the electro...
Article
Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In embryonic mouse cortical neurons using glucose as only fuel, activation by NMDA elicits a strong workload (ATP demand) dependent on Na+ and Ca2+ entry, and stimulates glucose uptake, glycolysis, pyruvate and lactate prod...
Article
Full-text available
AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named “early infantile epileptic encephalopathy 39” (EIEE 39, OMIM # 612949) charac...
Article
In addition to its uptake across the Ca²⁺ uniporter, intracellular calcium signals can stimulate mitochondrial metabolism activating metabolite exchangers of the inner mitochondrial membrane belonging to the mitochondrial carrier family (SLC25). One of these Ca²⁺-regulated mitochondrial carriers (CaMCs) are the reversible ATP-Mg²⁺/Pi transporters,...
Preprint
Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In cortical neurons using glucose as only fuel, activation by NMDA, which elicits a strong workload dependent on Na+ entry, stimulates glucose uptake, glycolysis, pyruvate and lactate production, and OXPHOS in a Ca2+-depend...
Article
Background In man two mitochondrial aspartate/glutamate carrier (AGC) isoforms, known as aralar and citrin, are required to accomplish several metabolic pathways. In order to fill the existing gap of knowledge in Drosophila melanogaster, we have studied aralar1 gene, orthologue of human AGC-encoding genes in this organism. Methods The blastp algor...
Article
Full-text available
The brain uses mainly glucose as fuel with an index of glucose to oxygen utilization close to 6, the maximal index if all glucose was completely oxidized. However, this high oxidative index, contrasts with the metabolic traits of the major cell types in the brain studied in culture, neurons and astrocytes, including the selective use of the malate-...
Article
The elevated energy demands in the brain are fulfilled mainly by glucose catabolism. In highly polarized neurons, about 10-50% of mitochondria are transported along microtubules using mitochondrial-born ATP to locations with high energy requirements. In this report, we have investigated the impact of Aralar deficiency on mitochondrial transport in...
Article
Full-text available
The pathology of Charcot-Marie-Tooth (CMT), a disease arising from mutations in different genes, has been associated with an impairment of mitochondrial dynamics and axonal biology of mitochondria. Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause several forms of CMT neuropathy, but the pathogenic mechanisms invol...
Article
Astrocytes respond to energetic demands by upregulating glycolysis, lactate production, and respiration. This study addresses the role of respiration and calcium regulation of respiration as part of the astrocyte response to the workloads caused by extracellular ATP and glutamate. Extracellular ATP (100 μM to 1 mM) causes a Ca²⁺‐dependent workload...
Article
Full-text available
Store-operated calcium entry (SOCE) is a Calcium (Ca2+) influx pathway activated by depletion of intracellular stores that occurs in eukaryotic cells. In neurons, the presence and functions of SOCE are still in question. Here, we show evidences for the existence of SOCE in primary mouse cortical neurons. Endoplasmic reticulum (ER)-Ca2+ depletion us...
Article
A series of simplex cases have been reported under various diagnoses sharing early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers, a distinctive facial gestalt, and prenatal and postnatal growth retardation. For historical reasons, we suggest naming the entity Fon...
Article
Full-text available
GDAP1 is an outer mitochondrial membrane protein involved in Charcot-Marie-Tooth (CMT) disease. Lack of GDAP1 gives rise to altered mitochondrial networks and endoplasmic reticulum (ER)-mitochondrial interactions resulting in a decreased ER-Ca2+ levels along with a defect on store-operated calcium entry (SOCE) related to a misallocation of mitochon...
Article
Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca(2+), regulation of metabolite transport by extramitochondrial Ca(2+) represents an alternative Ca(2+)-dependent mechanism to regulate mitochondrial function. The Ca(2+) regulated mitochondrial transporters (CaMCs) are well suited for that role, as the...
Article
Full-text available
The mitochondrial H(+)-ATP synthase synthesizes most of cellular ATP requirements by oxidative phosphorylation (OXPHOS). The ATPase Inhibitory Factor 1 (IF1) is known to inhibit the hydrolase activity of the H(+)-ATP synthase in situations that compromise OXPHOS. Herein, we demonstrate that phosphorylation of S39 in IF1 by mitochondrial protein kin...
Article
Glutamate excitotoxicity is caused by sustained activation of neuronal NMDA receptors causing a large Ca(2+) and Na(+) influx, activation of poly(ADP ribose) polymerase-1 (PARP-1), and delayed Ca(2+) deregulation. Mitochondria undergo early changes in membrane potential during excitotoxicity, but their precise role in these events is still controve...
Article
Calcium is thought to regulate respiration but it is unclear whether this is dependent on the increase in ATP demand caused by any Ca2 + signal or to Ca2 + itself. [Na+]i, [Ca2 +]i and [ATP]i dynamics in intact neurons exposed to different workloads in the absence and presence of Ca2 + clearly showed that Ca2 +-stimulation of coupled respiration is...
Article
Neuronal respiration is controlled by ATP demand and Ca(2+) but the roles played by each are unknown, as any Ca(2+) signal also impacts on ATP demand. Ca(2+) can control mitochondrial function through Ca(2+)-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix afte...
Article
In eukaryotic cells, the exchange of metabolites across the inner mitochondrial membrane is performed by members of the mitochondrial carrier family (MCF), the largest family of solute transporters. Mutations in MCF genes are associated with rare genetic diseases underscoring the relevance of individual MCF members. Mitochondrial carriers have a co...
Article
Full-text available
It has been known for a long time that mitochondria isolated from hepatocytes treated with glucagon or Ca2+-mobilizing agents such as phenylephrine show an increase in their adenine nucleotide (AdN) content, respiratory activity, and calcium retention capacity (CRC). Here, we have studied the role of SCaMC-3/slc25a23, the mitochondrial ATP-Mg/Pi ca...
Article
Full-text available
A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ve...
Article
Full-text available
Mitochondrial carriers (MC) form a highly conserved family involved in solute transport across the inner mitochondrial membrane in eukaryotes. In mammals, ATP-Mg/Pi carriers, SCaMCs, form the most complex subgroup with four paralogs, SCaMC-1, -2, -3 and -3L, and several splicing variants. Here, we report the tissue distribution and subcellular loca...
Data
Expression of SCaMC-1L throughout the spermatogenic stages. The germ cells present at each stage (I–XII) of the mouse spermatogenic cycle from intermediate spermatogonia (In) to mature sperm are pictured (adapted from [37]). Each stage of the spermatogenic cycle comprises a set of developing germ cells. In the diagram, the developmental progression...
Data
SCaMC-1 and SCaMC-1L non-annotated protein sequences used in this study. (alphabetical order of species). (DOCX)
Data
COS-7 cells were grown on glass plates and transiently transfected with SCaMC-1L-EGFP construct. The SCaMC-1L-EGFP expressing vector was obtained subcloning the full coding sequence (amino acids1–473) of mouse SCaMC-1L-1L into pEGFP-N. Images were taken every 15 min for 7 h using an Axiovert 200 (Zeiss) system at 37 C with a ×40 objective using a C...
Data
Ka/Ks ratios among mammalian SCaMC-1 and SCaMC-1L orthologues. To calculate Ka/Ks values for SCaMC-1 and SCaMC-1L genes we retrieved coding sequences corresponding to exons 2 to 7 of representative mammalian and performed pairwise sequence comparisons. The results are based on Ka/Ks values for sequences from seven representative mammals; Bos Taurus...
Data
Accession numbers of annotated SCaMC-1 and SCaMC-1L proteins. (alphabetical order of species). (DOCX)
Data
Perinuclear honeycomb-like SCaMC-1L aggregates. A representative image of SCaMC-1L-transfected COS-7 cells containing SCaMC-1L honeycomb-like aggregates is shown. SCaMC-1L was detected with specific anti-SCaMC-1L antibody visualized with a FITC-conjugated secondary antibody, mitochondrial structures are stained with anti-COX-I antibody visualized w...
Data
Alignment of SCaMC-1 and SCaMC-1L sequences encoded by exons 2 to 7 was performed with ClustalW program and coloured using BOXSHADE program. (www.ch.embnet.org). (TIF)
Data
The C-terminal does not affect the intracellular patterns of ScaMC-1L. (A) Representative images of SCaMC-1L-expressing COS-7 cells showing the different intracellular patterns observed; cytosolic (a), mitochondrial (b) and extra-mitochondrial aggregates (c). COS-7 cells were transfected with a full-length SCaMC-1L construct unchanged at C-end, co-...
Data
Cytosolic SCaMC-1L granules do not co-localize with late endosomal/lysosomal markers. COS-7 cells were transiently transfected with FLAG-tagged SCaMC-1L and 24–30 hours later co-localization was analyzed by co-staining with specific markers. COS-7 cells were co-stained with anti-SCaMC-1L antibody (A, B) and specific markers for late endosomes (A) a...
Article
The aralar/AGC1 knockout (KO) mouse shows a drastic decrease in brain aspartate and N-acetylaspartate levels and global hypomyelination, which are attributed to the lack of neuron-produced NAA used by oligodendrocytes as precursor of myelin lipid synthesis. In addition, these mice have a gradual drop in brain glutamine synthesis. We show here that...
Article
Full-text available
Ca(2+)-mediated mitochondrial permeability transition (mPT) is the final common pathway of stress-induced cell death in many major pathologies, but its regulation in intact cells is poorly understood. Here we report that the mitochondrial carrier SCaMC-1/SLC25A24 mediates ATP-Mg(2-)/Pi(2-) and/or HADP(2-)/Pi(2-) uptake into the mitochondria after a...
Conference Paper
Full-text available
The calcium-binding mitochondrial carriers of glutamate/aspartate (AGCs) and ATP-Mg/Pi (SCaMCs) provide a mechanism to transmit Ca2+ signals to mitochondria independent of the entry of calcium to the organelle. The AGCs Aralar/AGC1 and citrin/ AGC2 are components of the malate aspartate NADH shuttle and citrin is also a component of the urea cycle....
Article
In eukaryotes, cellular energy in the form of ATP is produced in the cytosol via glycolysis or in the mitochondria via oxidative phosphorylation and, in photosynthetic organisms, in the chloroplast via photophosphorylation. Transport of adenine nucleotides among cell compartments is essential and is performed mainly by members of the mitochondrial...
Article
S-resistin is a non-secretable resistin spliced variant described in white adipose tissue from Wistar rats. Since resistin has been implicated in adipogenesis regulation, here we have investigated the possible role of this new isoform in this process. For that, we have studied the adipocyte development in 3T3-L1 pre-adipocyte cell line stably expre...
Article
Two variants of the adipose hormone resistin are generated by alternative splicing in Wistar rats. Here we analyzed the expression of these resistin variants in 2 main visceral adipose depots, epididymal and retroperitoneal, as well as the resistin serum concentration during aging and food restriction. Total protein levels of resistin were also ana...
Article
The ADP/ATP and ATP-Mg/Pi carriers are widespread among eukaryotes and constitute two systems to transport adenine nucleotides in mitochondria. ADP/ATP carriers carry out an electrogenic exchange of ADP for ATP essential for oxidative phosphorylation, whereas ATP-Mg/Pi carriers perform an electroneutral exchange of ATP-Mg for phosphate and are able...
Article
Full-text available
Aralar, the mitochondrial aspartate-glutamate carrier present in beta-cells, is a component of the malate-aspartate NADH shuttle (MAS). MAS is activated by Ca2+ in mitochondria from tissues with aralar as the only AGC isoform with an S0.5 of approximately 300 nm. We have studied the role of aralar and its Ca2+-binding EF-hand motifs in glucose-indu...
Article
Full-text available
The SCaMCs (small calcium-binding mitochondrial carriers) constitute a subfamily of mitochondrial carriers responsible for the ATP-Mg/P(i) exchange with at least three paralogues in vertebrates. SCaMC members are proteins with two functional domains, the C-terminal transporter domain and the N-terminal domain which harbours calcium-binding EF-hands...
Article
Sal1p, a novel Ca2+-dependent ATP-Mg/Pi carrier, is essential in yeast lacking all adenine nucleotide translocases. By targeting luciferase to the mitochondrial matrix to monitor mitochondrial ATP levels, we show in isolated mitochondria that both ATP-Mg and free ADP are taken up by Sal1p with a K(m) of 0.20 +/- 0.03 mM and 0.28 +/- 0.06 mM respect...
Article
Aralar, the Ca(2+)-dependent mitochondrial aspartate-glutamate carrier expressed in brain and skeletal muscle, is a member of the malate-aspartate NADH shuttle. Disrupting the gene for aralar, SLC25a12, in mice has enabled the discovery of two new roles of this carrier. On the one hand, it is required for synthesis of brain aspartate and N-acetylas...
Article
Full-text available
Ca(2+) signaling in mitochondria is important to tune mitochondrial function to a variety of extracellular stimuli. The main mechanism is Ca(2+) entry in mitochondria via the Ca(2+) uniporter followed by Ca(2+) activation of three dehydrogenases in the mitochondrial matrix. This results in increases in mitochondrial NADH/NAD ratios and ATP levels a...
Article
Full-text available
Sal1p is a mitochondrial protein that belongs to the SCaMC (short calcium-binding mitochondrial carrier) subfamily of mitochondrial carriers. The presence of calcium-binding motifs facing the extramitochondrial space allows the regulation of the transport activity of these carriers by cytosolic calcium and provides a new mechanism to transduce calc...
Article
Invertebrate metallothioneins (MT) have mainly been reported in digestive tissues, but data about the existence of a ubiquitous isoform expressed also in nervous tissue, are not available. Here we report the identification of a new metallothionein gene (MTPA) from the lobster Panulirus argus, putatively encoding a 59 residue polypeptide including 1...
Article
The transport of metabolites, nucleotides and cofactors across the mitochondrial inner membrane is performed by members of mitochondrial carrier family (MCF). These proteins share marked structural features that have made feasible the functional characterization of numerous MCs in the last years. The MCs responsible for transport activities in mito...
Article
Full-text available
Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, involved in the transport of aspartate from mitochondria to cytosol, and in the transfer of cytosolic reducing equivalents into mitochondria as a member of the malate-aspartate NADH shuttle. In the present study, we describe the...
Article
CaMCs (calcium-dependent mitochondrial carriers) represent a novel subfamily of metabolite carriers of mitochondria. The ATP-Mg/P(i) co-transporter, functionally characterized more than 20 years ago, has been identified to be a CaMC member. There are three isoforms of the ATP-Mg/P(i) carrier in mammals, SCaMC-1 (short CaMC-1), -2 and -3 (or APC-1,...
Article
Full-text available
The NADH shuttle system, which transports reducing equivalents from the cytosol to the mitochondria, is essential for the coupling of glucose metabolism to insulin secretion in pancreatic beta cells. Aralar1 and citrin are two isoforms of the mitochondrial aspartate/glutamate carrier, one key constituent of the malate-aspartate NADH shuttle. Here,...
Article
Full-text available
Aralar1 and citrin were identified as calcium binding aspartate/glutamate carriers (AGC) in mitochondria. The presence of calcium binding motifs facing the extramitochondrial space allows the regulation of the transport activity of these carriers by cytosolic calcium and provides a new mechanism to transduce calcium signals in mitochondria without...
Article
Full-text available
Resistin is a secreted adipose tissue hormone that belongs to the resistin-like molecule family. We report here a new alternatively spliced isoform of the rat resistin gene, named S-resistin (short resistin), detected in adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). A comparison of this cDNA variant and genomic sequenc...
Article
Full-text available
The malate-aspartate NADH shuttle in mammalian cells requires the activity of the mitochondrial aspartate-glutamate carrier (AGC). Recently, we identified in man two AGC isoforms, aralar1 and citrin, which are regulated by calcium on the external face of the inner mitochondrial membrane. We have now identified Agc1p as the yeast counterpart of the...
Conference Paper
Full-text available
Hemos identificado la proteína Agc1p como el homólogo en S. cerevisiae del transportador de aspartato-glutamato (AGC) humano, requerido para el funcionamiento de la lanzadera de NADH de malato-aspartato en mamíferos. En colaboración con el grupo de F. Palmieri (Univ. Bari), la proteína fue sobreexpresada en bacterias y en mitocondrias de levadura y...
Article
Aralar1 and citrin are two isoforms of the mitochondrial carrier of aspartate-glutamate (AGC), a calcium regulated carrier, which is important in the malate-aspartate NADH shuttle. The expression and cell distribution of aralar1 and citrin in brain cells has been studied during development in vitro and in vivo. Aralar1 is the only isoform expressed...
Article
Aralar1 and citrin are members of the subfamily of calcium-binding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC). These proteins are activated by Ca2+ acting on the external side of the inner mitochondrial membrane. Although it is known that aralar1 is expressed mainly in skeletal muscl...
Article
The present report describes the expression profiles of different tissues and developmental changes of mouse aspartate/glutamate carrier (AGC) genes, Slc25a13 and Slc25a12, and an ornithine transporter gene, Ornt1, in relation to urea cycle enzyme genes, carbamoylphosphate synthetase I (CPS) and argininosuccinate synthetase (ASS). Slc25a13 encodes...
Article
Full-text available
The mitochondrial aspartate/glutamate carrier catalyzes an important step in both the urea cycle and the aspartate/malate NADH shuttle. Citrin and aralar1 are homologous proteins belonging to the mitochondrial carrier family with EF-hand Ca(2+)-binding motifs in their N-terminal domains. Both proteins and their C-terminal domains were overexpressed...
Article
Full-text available
We have recently identified a subfamily of mitochondrial carriers that bind calcium, and cloned ARALAR1, a member of this subfamily expressed in human muscle and brain. We have now cloned a second human ARALAR gene (ARALAR2) coding for a protein 78.3% identical to Aralar1, but expressed in liver and non-excitable tissues. Aralar2 is identical to ci...
Article
Full-text available
Neural stem cell lines represent a homogeneous source of cells for genetic, developmental, and gene transfer and repair studies in the nervous system. Since both gene transfer of neurotrophic factors and cell replacement strategies are of immediate interest for therapeutical purposes, we have generated BDNF-secreting neural stem cell lines and inve...
Conference Paper
Full-text available
La superfamilia de transportadores mitocondriales contiene una nueva subfamilia caracterizada por la presencia de dominios de unión de calcio de tipo manos EF con miembros en Saccharomyces cerevisiae, Caenorhabditis elegans y varias especies de mamífero. Todos ellos tienen una estructura bipartita: la mitad carboxilo terminal tiene los rasgos disti...
Article
Full-text available
We have identified a new calcium-dependent subfamily of mitochondrial carrier proteins with members in Saccharomyces cerevisiae, Caenorhabditis elegans, and various mammalian species. The members of this subfamily have a bipartite structure: a carboxyl-terminal half with the characteristic features of the mitochondrial solute carrier superfamily an...
Conference Paper
We have identified a new calcium-dependent subfamily of mitochondrial carrier proteins with members in Saccharomyces cerevisiae, Caenorhabditis elegans and various mammalian species. The members of this subfamily have a bipartite structure: a carboxy-terminal half with the characteristic features of the mitochondrial solute carrier superfamily and...