Jose Luis Cabrera Alarcón, PhD
I joined GENOXPHOS group to develop and strength the bioinformatic lines of investigation. Mitochondrial respiratory complexes are precise protein machines, in which any mismatch can have bioenergetic consequences. Bearing this in mind, the diploid condition of nuclear OXPHOS genes represents an unexplored potential source of functional variability within the OXPHOS components. I am exploring this possibility supported by a Human Frontier Science Program (HSFP) project. I am investigating the existency of potential mechanisms for the regulation of the expression of alternative alleles. This implies the development of ad hoc methodology for the analysis of single cell RNAseq data. In addition, I am developing a pipeline of in silico models of the respiratory chain complexes to estimate the structural and functional effect of specific aminoacidic changes.
Carolina García-Poyatos, PhD
After defending my doctoral thesis at the University of Bern, Switzerland, I joined the CNIC in 2020 to finish a cooperative project between the GENOXPHOS group and the group led by Dr. Mercader. In 2021, I definitively joined the GENOXPHOS group as a postdoctoral researcher, forming part of the CIBERFES network. Here, I develop a project to elucidate the physiological relevance of alternative isoforms of the COX7a subunit (COX7A1, COX7A2 AND COX7A2L or SCAF1) of cytochrome c oxidase or complex IV (CIV). CIV catalyzes the last step in the mitochondrial electron transport chain by transferring electrons from cytochrome c to oxygen and forming water. The CIV can be found in monomeric form, dimers, multimers, and super-assembled in other complexes that are part of the Q-respirasome and the N-respirasome (Cogliati and Calvo, et al. Nature 2016). Using zebrafish and mouse models, I study the role of supramolecular structures of CIV at the molecular and physiological level, focusing on muscle pathophysiology and cardiac regeneration.
Cogliati and Calvo, et al. Nature 2016
Garcia-Poyatos et al. EMBO Rep. 2020
Pablo Hernansanz Agustín, PhD
My research is focused on the role of Na+ in the regulation the oxidative phosphorylation system related to the formation of supercomplexes, ubiquinone and cytochrome c dynamics and pool behaviour, electron flux and the production of reactive oxygen species (ROS). We recently published that Na+ can act as a second messenger by regulating the inner mitochondrial membrane (IMM) fluidity, lowering the electron transfer from complex II to complex III, but not inside supercomplexes, and increasing the production of ROS by complex III. This mechanism controls acute hypoxic adaptations such as hypoxic pulmonary vasoconstriction. Actually, I am exploring the implication of this pathway in the onset and/or development of a variety physiological and pathophysiological scenarios.
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, 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 possible cardioprotective effect of inhibiting Fgr to reduce cardiac inflammation.
María Concepción Jiménez Gómez, PhD
I joined GENOXPHOS group after a first step in my career working in the pharma industry. I am aimed to explore and develop the translational potential of the basic research discoveries of the group by identifying potential pharmacological targets and develop genetic tools of potential use in the treatment of human diseases. In addition, my work is focused on the development and assessment of translational potential and patentability of techniques and know-how of the group developed in the group to make them available to industry partners. GENOXPHOS is currently developing projects with leaders in the pharmaceutical industry, including Astrazeneca and Minovia Therapeutics.
Andréa Curtabbi, MD
I joined GENOXPHOS lab after obtaining my MD degree from the University of Turin. My research is focused in understanding how dysfunction in oxidative phosphorylation affects human health. By using mouse models of Leigh syndrome, a heritable mitochondrial disorder, I am investigating how genetic defects respiratory complexes lead to neuromuscular pathologies. In collaboration with the proteomic unit at CNIC, I am looking for candidate genes that are important for respiratory complex I stability and activity that may have a role in human disease. I am also studying the role of ATP synthase oligomerization in mitochondrial cristae ultrastructure and tissue homeostasis.
Yolanda Martí Mateos
Yolanda Martí graduated in Biochemistry at the Universidad Autónoma de Madrid in 2016. During her Master’s studies she joined José Antonio Enríquez’s lab, where she worked on the supercomplexes’ assembly regulation. Currently, she is a PhD student studying the effects of the ablation of the mitochondrial regulatory protein OMA1, that participates in the control of mitochondrial structure, in the activation of the integrated stress response and, eventually, in the cell’s entry to apoptosis. In 2018, our group demonstrated that the absence of this protein in three models of heart failure preventively results in cardioprotection. Therefore, our current efforts are focused in proving the therapeutic potential of this target and exploring the possible adverse effects that the absence of this protein might have, due to the marked translational nature of this project.
Raquel Justo Méndez
I am performing my PhD on the variability of mitochondrial DNA (mtDNA) and its effect in the OXPHOS system behavior and mitochondrial ROS (mtROS) generation. Recent results of GENOXPHOS group demonstrate that different combinations of nuclear DNA and mitochondrial DNA promote differences in mitochondrial electron‐transport‐chain and thus, in oxidative phosphorylation performance. My research is focused on how the mitochondrial genetics and different mitochondrial metabolic signatures impacts in the global process of ageing and frailty. By using a mouse model of deficient in the proofreading capacity of the mitochondria DNA polymerase we also explore how different mitochondrial function affect the aging process.
Carmen Morales Vidal
After graduating in Biochemistry and Biomedical Sciences at the University of Valencia in 2020, I joined Genoxphos group as a master's student and, finally, as a predoctoral researcher. The main objective of my thesis project is to study the functional role of supercomplexes that do not allow electron transfer to oxygen by themselves and whose function, therefore, has no obvious relation with the efficiency of oxidative phosphorylation. Thus, my work focuses on two non-respirasome supercomplexes, I+IV and I+III2. Regarding I+IV, we propose that this understudied supercomplex might function as an oxygen sensor, somehow participating in the detection of low oxygen levels in the cell. This hypothesis is based on the fact that I+IV contains both complex IV, which binds oxygen and whose function is affected by oxygen availability, and complex I, which is known to undergo an active/deactive conformational change that triggers ROS production under hypoxia. Regarding I+III2, my work aims to shed light on the controversial existence of separate ubiquinone pools, a general one, available to free complexes and other enzymes, and others confined within supercomplexes and essentially used by its constituents. Then, I am generating mutants in the interaction between I and III to study the biological implications of having a unique ubiquinone pool, which, together with the mutation in Scaf1, the factor mediating super-assembly between III and IV, will allow me to construct the fluid model of the respiratory chain.
Xiaotong Hong is a PhD student from Pompeu Fabra University (UPF), co-directed by Dr. Pura Muñoz-Cánoves. In her PhD project, she aims to understand the role of mitochondrial dynamics in muscle stem cell (also called satellite cells) during muscle regeneration. Mitochondrial dynamics is regulated by various dynamin-family proteins such as mitofusin 1 (MFN1), optic atrophy 1 (OPA1) and dynamin-related protein 1 (DRP1). Loss of function of these proteins can lead to disturbed mitochondrial morphology and function. By ablating these mitochondrial-shaping proteins in satellite cells and studying the muscle regeneration upon injury, we can decipher how mitochondrial dynamics in the stem cells affects the regeneration of the tissue.
Macarena de Andrés Laguillo
Despite being one of the cell types with the highest oxygen availability, endothelial cells have a highly anaerobic metabolism. For years the role of the electronic transport chain in blood vessel development (angiogenesis) was considered little more than anecdotal, a dogma that has begun to be questioned in recent years.
My project, under the direction of Rui Benedito and co-direction of José Antonio Enríquez, focuses on characterizing how alterations in mitochondrial metabolism and the production of reactive oxygen species (ROS) affect and modulate angiogenesis in both physiological and pathological contexts.
The cross-sectional presence of angiogenesis in various pathologies (cancer, stroke, heart attacks, malformations, etc.) makes the understanding of the processes that govern it, something highly valued and necessary in the treatment of these diseases.
This project will take advantage of the experience of both groups using advanced genetic models, such as functional mosaics, to carry out a deep and detailed characterization of the mechanisms that underlie the mitochondrial modulation of angiogenesis.
Esther García Domínguez
I graduated in Physical Activity and Sports Sciences and am doing a PhD in Exercise Physiology in the FRESHAGE group of the University of Valencia. My thesis project focuses on studying the molecular mechanisms responsible for geriatric frailty syndrome and the possible interventions that prevent, delay or reverse its appearance, as well as identify early biomarkers of frailty that allow its early detection and aid in its clinical diagnosis. Mainly, I study physical exercise programs, both in humans and in animal experimental models, and the role of glucose-6-phosphate dehydrogenase as strategies against frailty.
I joined the GENOXPHOS group as visiting scientist during my second year of doctorate to start a collaboration with the Valencia group. This allows me to study the implication of mitochondrial structural and functional changes in the appearance and progression of frailty, as well as to know if interventions for the prevention and treatment of frailty have an effect on the function and content of mitochondria.
Raquel Martínez de Mena, PhD
I completed my Doctoral Thesis in Science at the Universidad Autónoma de Madrid and performed several years of laboratory work at the IIB in Madrid. Then I joined the GENOXPHOS group at CNIC as a technician specialized in cell culture and biochemical and molecular biology techniques.
Modified from Sci Adv. 2020 Jul 29;6(31)
María del Mar Muñoz Hernández
I joined GENOXPHOS after finishing my training as laboratory technician. In the group I am responsible for several aspects of the research with special expertise in handling experimental animal models including husbandry breeding and genetic characterization and with special training in surgery, metabolic and behavioral analysis.
Eva Raquel Martínez
I joined GENOXPHOS after several years of work in different research laboratories. I am working as a technician with special expertise in histological analysis to visualize cellular damage in different tissues. I am trained also in molecular biology methods and in handling experimental animal models.