Neuroenergetics and Metabolism Group

Our group is devoted to understanding how the metabolic flexibility of astrocytes impact on neuronal function and organismal higher-order behaviors. The brain has almost no energy reserve but its activity coordinates organismal function, a burden that requires precise coupling between neurotransmission and energy metabolism. Deciphering how the brain accomplishes this complex task is crucial to understand central facets of human physiology and disease mechanisms.

Each type of neural cell displays a peculiar metabolic signature, forcing the intercellular exchange of metabolites that serve as both energy precursors and paracrine signals. The paradigm of this biological feature is the astrocyte-neuron couple, in which the glycolytic metabolism of astrocytes contrasts with the mitochondrial oxidative activity of neurons. Disruption of this metabolic cooperation may contribute to the initiation or progression of several neurological diseases, thus requiring innovative therapies to preserve brain energetics.

Recently we have observed that, besides glucose, astrocytes avidly use fatty acids via mitochondrial ß-oxidation, a feature that allow these cells to keep mitochondrial complex I partially disassembled from complex III. By maintaining this conformation of the mitochondrial respiratory chain, fatty acids utilization in astrocytes allows enhanced mitochondrial reactive oxygen species (mROS) to drive neuronal functions via the modulation of specific molecular targets.

By combining genetic, biochemical and behavioral approaches, our laboratory is therefore dedicated to deciphering the molecular players involved in the regulation of brain cells metabolism that impact on organismal behaviors in health and disease.

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Group members

Juan Pedro Bolaños Full Professor (USAL)
Emilio Fernández Associate Professor (USAL)
Daniel Jiménez-Blasco Postdoctoral CIBERFES
Darwin Israel Manjarrés Raza Predoctoral JCYL
Sara Yunta Predoctoral JCYL
Darío García Rodríguez Predoctoral FPI
Luisa Hidalgo López Predoctoral FPU
Marta Antequera Duwell Predoctoral FPI
Davide Passaro Predoctoral MSCA
Thomas Zanettin Predoctoral MSCA
Paula Martín Marfil Predoctoral USAL
Estefanía Prieto Lab Technician
Mónica Resch Lab Technician


Juan Pedro Bolaños
Laboratory 2.10

Recent publications

Jimenez-Blasco D, Agulla J, Lapresa R, Garcia-MaciaM, Bobo-Jimenez V, Garcia-Rodriguez D, Manjarres-Raza I, Fernandez E, Jeanson Y, Khoury S, Portais J-C, Padro D, Ramos-Cabrer P, Carmeliet P, Almeida A, Bolaños JP.
Weak neuronal glycolysis sustains cognition and organismal fitness.
Nature Metabolism. In press
Morant-Ferrando B, Jimenez-Blasco D, Alonso-Batan P, Agulla J, Lapresa R, Garcia-Rodriguez D, Yunta-Sanchez S, Lopez-Fabuel I, Fernandez E, Carmeliet P, Almeida A, Garcia-Macia M, Bolaños JP.
Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition.
Nature Metabolism. 5:1290-1302 (2023)
Doi: 10.1038/s42255-023-00835-6
Lopez-Fabuel I, Garcia-Macia M, Buondelmonte C, Burmistrova O, Bonora N, Alonso-Batan P, Morant-Ferrando B, Vicente-Gutierrez C, Jimenez-Blasco D, Quintana-Cabrera R, Fernandez E, Llop J, Ramos-Cabrer P, Sharaireh A, Guevara-Ferrer M, Fitzpatrick L, Thompton CD, McKay TR, Storch S, Medina DL, Mole SE, Fedichev PO, Almeida A, Bolaños JP.
Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis.
Nature Communications. 13:536 (2022)
Doi: 10.1038/s41467-022-28191-1
Jimenez-Blasco, D., Busquets-Garcia, A., Hebert-Chatelain, E., Serrat, R., Vicente-Gutierrez, C., Ioannidou, C., Gómez-Sotres, P., Lopez-Fabuel, I., Resch-Beusher, M., Resel, E., Arnouil, D., Saraswat, D., Varilh, M., Cannich, A., Julio-Kalajzic, F., Bonilla-Del Río, I., Almeida, A., Puente, N., Achicallende, S., Lopez-Rodriguez, M.-L., Jollé, C., Déglon, N., Pellerin, L., Josephine, C., Bonvento, G., Panatier, A., Lutz, B., Piazza, P.-V., Guzmán, M., Bellocchio, L., Bouzier-Sore, A.-K., Grandes, P., Bolaños JP*, Marsicano, G*. (*co-supervisor and co-corresponding authors)
Glucose metabolism links astroglial mitochondria to cannabinoid effects.
Nature. 583(7817):603-608 (2020)
Doi: 10.1038/s41586-020-2470-y
Vicente-Gutierrez C#, Bonora N#, Bobo-Jimenez V, Jimenez-Blasco D, Lopez-Fabuel I, Fernandez E, Josephine C, Bonvento G, Enriquez JA, Almeida A and Bolaños JP.
Astrocytic mitochondrial ROS modulate brain metabolism and mouse behavior.
Nature Metabolism. 1:201-2011 (2019) (#co-first authors)
Doi: 10.1038/s42255-018-0031-6
Lopez-Fabuel I, Le Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A and Bolaños JP.
Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.
Proc. Natl. Acad. Sci. U.S.A. 113: 13063-13068 (2016)
Doi: 10.1073/pnas.1613701113

Proyectos de investigación

Agencia Estatal de Investigación (PID2022-138813OB-I00)
Marie Sklodowska-Curie Action (101072759)
Caixa Research (LCF/PR/HR23/52430016)