Jose Luis Cabrera Alarcón, PhD
Over the course of five years as a postdoctoral researcher in the GENOXPHOS group, we have unified evolutionary, population and structural information related to the components of Oxidative Phosphorylation (OxPhos) to allow a better understanding of the genetics and fitness of the system.
![Jose Luis Cabrera Alarcón, PhD](https://www.cnic.es/sites/default/files/administrator/variability-map-in-oxphos-system.png)
Pablo Hernansanz Agustín, PhD
My research is focused on the role of Na+ in the regulation the oxidative phosphorylation (OXPHOS) system related to bioenergetics, electron flux and the production of reactive oxygen species (ROS), as well as the relationship of all of them with mitochondrial diseases. We have recently discovered that Na+ establishes a gradient across the inner mitochondrial membrane, constituting up to 50% of the membrane potential in coupled respiring mitochondria. The mitochondrial Na+ gradient is set by a non-canonical activity of mitochondrial complex I, a Na+/H+ antiporter function. Indeed, mutations in this complex, only affecting the Na+ exchanger activity, are related to neurodegenerative diseases. We are currently exploring how this activity is related to a broad spectrum of (patho)physiological conditions and trying to understand the implications of the de-regulation of this activity in human health.
![Pablo Hernansanz Agustín, PhD image](https://www.cnic.es/sites/default/files/administrator/pablo-hernansanz.png)
Marta Pérez-Hernández Durán, PhD
After defending my PhD at the University Complutense of Madrid (Spain) and my first postdoctoral fellowship at New York University (U.S.) studying various cardiomyopathies, I joined the GENOXPHOS group to study the role of the tyrosine kinase Fgr in the heart.
Previous studies in our laboratory have shown that Fgr, in the mitochondria, upon stress, phosphorylates complex II of the electron transport chain. This leads to a change in the metabolism of the cell, which ultimately leads to inflammation.
My project studies the cardioprotective effect of Fgr inhibition (genetically or pharmacologically) to reduce cardiac inflammation. Our results could then serve as a foundation to explore treatment of other cardiac conditions in which an inflammatory component plays an important role such as myocardial infarction, atherosclerosis or arrhythmogenic right ventricular cardiomyopathy. In the latter, in collaboration with Prof. Delmar (New York University) we have observed that Fgr inhibition in vitro is protective.
María Concepción Jiménez Gómez, PhD
After obtaining a doctorate in Molecular Biology from the UAM, I began working in the Research and Development department of the biotechnology company Zeltia SAU. In 2010 I decided to refocus my professional career and joined Genoxphos group led by Dr. Enríquez's at CNIC. During the last few years, I have managed the group's projects, as well as the translational development initiatives of basic research discoveries. The Genoxphos group collaborates on projects with leaders in the pharmaceutical industry, including Astrazeneca and Minovia Therapeutics. Also, based on my research training, I participate in the supervision of students hosted by the group, as well as in the co-direction of Yolanda Martí's doctoral thesis, (manuscript in preparation).
Raquel Justo Méndez
I am biologist (Universidad Autónoma de Madrid) currently performing my phD in Molecular Biomedicine under the supervision of José Antonio Enríquez and Ana Victoria Lechuga-Vieco in which we are evaluating the impact of mito-nuclear crosstalk during hematopoiesis under conditions of normal vs. high mitochondrial variability. Our study involves immune, metabolic, and mitochondrial profiling, focusing on aspects such as ROS management, organization of respiratory complexes, and fuel preference.
By using a mouse model deficient in the proofreading capacity of the mitochondrial DNA polymerase we shed light on how immune cells contribute to inflammaging, frailty and age-related phenotypes, emphasizing the significance of mitochondrial quality control and translation mechanisms.
![Raquel Justo Méndez image](https://www.cnic.es/sites/default/files/administrator/raquel-justo.png)
Carmen Morales Vidal
After graduating in Biochemistry and Biomedical Sciences at the University of Valencia in 2020, I joined the Genoxphos group as a Master’s student and finally as a predoctoral researcher at the end of 2021. My thesis project seeks to understand the reason behind the superassembly of mitochondrial complexes I (CI) and III (CIII), an interaction that is highly conserved in nature, from yeast to mammals, and that gives rise to supercomplexes such as I+III2 and I+III2+IV. Several functions have been proposed for this association, including the channeling of the substrate, ubiquinone, from one complex to the other and the reduction of reactive oxygen species production. In order to further study the role of the I+III2 interaction in the functioning of the respiratory chain and mitochondrial and cellular metabolism, I am currently generating cell lines in which the interaction between CI and CIII is disrupted. This work material will be the starting point to study the importance of the I+III2 interaction in living beings.
Macarena de Andrés Laguillo
VHL disease, a genetic disorder, manifests in vascular tumors called hemangioblastomas, primarily found in the retinas and brains of patients. Our research delves into the molecular mechanisms driving their development. Employing a mouse genetic model, we aim to unravel how different cell types, both endothelial and non-endothelial, contribute to hemangioblastoma formation. We've discovered that VHL-deficient cells, with their altered metabolism, influence the behavior of neighboring cells. Additionally, we're investigating the role of hypoxia-inducible factor 2 (HIF2) in this process.
Raquel Martínez de Mena, PhD
After completing my PdD in Sciences at the Universidad Autónoma de Madrid and after performing several years of research on brown adipose tissue and thyroid hormones at the IIB Alberto Sols in Madrid, I joined Dr José Antonio Enriquez´s group to work as a technician specialized in cell culture and biochemical and molecular biology techniques in the field of Functional Genetics of the Oxidative Phosphorylation System.
I support and participate in several group projects.
![Raquel Martínez de Mena, PhD image](https://www.cnic.es/sites/default/files/administrator/image016.png)
Modified from Sci Adv. 2020 Jul 29;6(31)
María del Mar Muñoz Hernández
I joined the GENOXPHOS group after finishing my training as a laboratory technician, and I am currently completing my academic training with a Biology degree at Universidad Autónoma de Madrid.
In the group I am responsible for various aspects of research, focusing on experimental animal models, including breeding and genetic characterization of these. I also have special training in surgery (especially cardiac) and metabolic and behavioral analysis in aging.
![María del Mar Muñoz Hernández image](https://www.cnic.es/sites/default/files/administrator/image017.png)
Eva Raquel Martínez
As a laboratory technician, I am responsible for conducting experiments, analyzing samples, and performing tests in a laboratory. My role often involves using various scientific instruments and ensuring accurate recording of data for research or diagnostic purposes.
These techniques range from DNA genotyping to the treatment of tissue samples with fine diagnostics.
![Eva Raquel Martínez image](https://www.cnic.es/sites/default/files/administrator/image019.png)
Marina Rosa Moreno
My thesis project is based on the structural study of electronic transport chain complexes using in silico models of these proteins.
With computational tools we are able to model the folding of proteins in the electronic transport chain, which have subunits encoded in both nuclear and mitochondrial DNA; and, using these models, predict the effect that mutations, incorporation of ligands or binding to other proteins may have on the structure of the protein.
I am currently doing a research stay at the Dana Farber Cancer Institute in Boston, MA. The objective of this stay is to train me in the use of electron cryomicroscopy to obtain models of mitochondrial supercomplexes with which to better understand their behavior and functionality in different conditions.
Paula Fernández-Montes
After graduating in Biology at the Universidad Autónoma de Madrid, I joined the GENOXPHOS group as a master student and finally as a predoctoral researcher. In my second year, I study the role of alternative isoforms of complex IV, specifically the Cox7a family. Complex IV (cytochrome oxidase c) is the last complex in the electron transport chain and undergoes a high level of regulation. The COX7A family is formed by different isoforms: COX7A1, COX7A2 and COX7A2L or SCAF1 and they are interchangeable. The alternative Cox7a subunits confer to complex IV different supramolecular organization, appearing in monomeric, dimer, multimer and super-assembled with other complexes forming the Q-respirasome and the N-respirasome (Cogliati and Calvo, et al. Nature 2016).
Using murine and cellular models, we have observed that the supramolecular structures of complex IV have different metabolic and physiological functions, ranging from organism viability, metabolic maturation necessary for proper tissue physiology, to plasticity and adaptation to different metabolic requirements.
Michaela Veliova
I joined the GENOXPHOS lab in 2022 as a postdoctoral researcher, after finishing my PhD at the University of California, Los Angeles. My research focuses on the intracellular heterogeneity of cardiomyocyte mitochondria, which are segregated into functionally distinct mitochondrial types (or mitotypes), the interfibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM). While the functional distinctions and physiological relevance of cardiomyocyte mitotypes are well-accepted and extensively researched, it is still unclear by which mechanism these two distinctive mitochondrial populations can be generated and maintained within a single cell. Therefore, my project aims to understand the regulation of differential protein expression in cardiomyocyte mitotypes.
Rebeca Acín
Even though I have been studying mitochondria and its role in orchestrating cellular metabolism for 25 years, I am still surprise of the many unknowns where mitochondria is not only the “brain” but also the “executor arm”. Now that I’m back at CNIC, my research line will be focused in studying the role of ATP depletion in the context of heart failure. ATP depletion, due to increase in ATP hydrolytic capacity, is a common metabolic consequence of mitochondrial deficiencies. Our group has recently demonstrated that Complex V ATP hydrolysis inhibition is beneficial in mitochondrial derived pathologies. Exploring the role of ATP hydrolysis in heart failure and being able to target it, will open new therapeutic pathways to treat cardiovascular diseases.
Sara Natalia Jaroszewicz
I graduated in Biochemistry at the Universidad Autónoma de Madrid in 2022 and joined the GENOXPHOS group in the summer of that same year as a CICERONE internship student, and later as a Master’s student. A few months ago I started my PhD thesis with the aim of deciphering the in situ organization of the electron transport chain with super-resolution techniques.
Mitochondria are essential organelles in eukaryotic cell metabolism. Inside mitochondria, oxidative phosphorylation takes place, mediated by enzymes called respiratory complexes (RCs), which can assemble into macromolecular structures known as supercomplexes (SCs). Although the existence of SCs has been demonstrated in many studies employing very diverse techniques, there are still questions about how these complexes are actually organized in the inner mitochondrial membrane and how a change in the ratio of free RCs to SCs could influence the development of cardiac disease. To answer these questions, my project will focus on optimizing STED, Expansion Microscopy and cryoET super-resolution methods in order to visualize SCs simultaneously in situ, to determine their physiological position in subdomains of mitochondrial cristae, and to compare them quantitatively in a murine model of heart failure.