We are pleased to welcome Juan P. Bolaños from the Institute of Functional Biology and Genomics (IBFG), University of Salamanca in Spain, on November 6th invited by Julien Courchet.

He will give a seminar at 11am entitled: “ Beyond energy: astrocytic mitochondria as signals for behaviour ”

 📍 The seminar will take place in the Physics Amphitheatre, on the ground floor.

ABSTRACT

Different brain cell types exhibit distinct metabolic signatures that link energy economy to cellular function. Astrocytes and neurons, for instance, diverge dramatically in their reliance on glycolysis versus oxidative phosphorylation, underscoring that metabolic fuel efficiency is not uniform across cell types. A key factor shaping this divergence is the structural organization of the mitochondrial respiratory chain into supercomplexes. Specifically, complexes I (CI) and III (CIII) form a CI–CIII supercomplex, but the degree of this interaction varies by cell type. In neurons, CI is predominantly integrated into supercomplexes, resulting in highly efficient mitochondrial respiration and minimal reactive oxygen species (ROS) generation. Conversely, in astrocytes, a larger fraction of CI remains freely existing, apart from CIII, leading to reduced respiratory efficiency and elevated mitochondrial ROS production. This modular architecture enables astrocytes to support neuronal health and influence complex organismal behaviors. Furthermore, metabolic reprogramming in astrocytes, such as enhanced fatty acid oxidation, reinforces this pattern. Our studies show that loss of the key rate-limiting step in fatty acid ß-oxidation, CPT1A, in astrocytes increases CI–CIII supercomplex formation, reducing ROS and impairing cognitive performance. This underscores how supercomplex interactions shapes both energetic efficiency and redox signaling, with broader consequences supporting neural activity, intercellular cooperation, overall brain adaptability and behaviour.

 

MAIN PUBLICATIONS

1. Jimenez-Blasco D, Agulla J, Lapresa R, Garcia-Macia M, Bobo-Jimenez V, Garcia-Rodriguez D, Manjarres-Raza I, Fernandez E, Jeanson Y, Khoury S, Portais JC, Padro D, Ramos-Cabrer P, Carmeliet P, Almeida A & Bolaños JP. Weak neuronal glycolysis sustains cognition and organismal fitness.

Nature Metabolism 6:1253-1267 (2024) (doi: 10.1038/s42255-024-01049-0) (highlighted in N&V)

2. 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) (highlighted in N&V)

3. 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)

4. Soldati C, Lopez-Fabuel I, Wanderlingh LG, Garcia-Macia M, Monfregola J, Esposito A, Napolitano G, Guevara-Ferrer M, Scotto Rosato A, Krogsaeter EK, Paquet D, Grimm CM, Montefusco S, Braulke T, Storch S, Mole SE, De Matteis MA, Ballabio A, Sampaio JL, McKay T, Johannes L, Bolaños JP* & Medina DL* (*co-corresponding authors). Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype.

EMBO Molecular Medicine e13742 (2021) (doi.org/10.15252/emmm.202013742)

5. Bonvento G & Bolaños JP. Astrocyte-neuron metabolic cooperation shapes brain activity.

Cell Metabolism 33:1546-1564 (2021) (doi.org/10.1016/j.cmet.2021.07.006)

6. Jimenez-Blasco D, Busquets-Garcia A, Hebert-Chatelain E, Serrat R, Vicente-Gutierrez C, Lopez-Fabuel I, Resch M, Resel E, Saraswat D, Varilh M, Cannich A, Bonilla-Del Rio I, Bellocchio L, Almeida A, Puente N, Lopez-Rodriguez ML, Lutz B, Piazza PV, Guzman M, Bouzier-Sore AK, Grandes P, Bolaños JP* & Marsicano G* (*co-senior & co-corresponding authors). Glucose metabolism links astroglial mitochondria to cannabinoid effects.

Nature 583:603-608 (2020) (doi.org/10.1038/s41586-020-2470-y) (highlighted in News & Views)

7. Vicente-Gutierrez C, Bonora N, Bobo-Jimenez V, Jimenez-Blasco D, Lopez-Fabuel I, Fernandez E, Josephine C, Bonvento G, Enriquez JA, Almeida A & Bolaños JP. Astrocytic mitochondrial ROS modulate brain metabolism and mouse behavior.

Nature Metabolism 1:201-211 (2019) (doi:10.1038/s42255-018-0031-6)

8. Lopez-Fabuel I, Le Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A & Bolaños JP. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.

Proc. Natl. Acad. Sci. USA 113:13063-13068 (2016) (doi: 10.1073/pnas.1613701113)

9.          Requejo-Aguilar R, Lopez-Fabuel I, Fernandez E, Martins LM, Almeida A & Bolaños JP. PINK1 deficiency sustains cell proliferation by re-programming glucose metabolism through HIF1.

Nature Communications 5:4514 (2014) (doi: 10.1038/ncomms5514)

10. Quintana-Cabrera R, Fernandez S, Bobo V, Garcia-Escobar J, Sastre J, Almeida A & Bolaños JP. g-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor.

Nature Communications 3: 718 (2012) (doi: 10.1038/ncomms1722)