MacPhagy Lab

Our scientific interests are closely tied to autophagy, the main recycling system of the cell. Autophagy regulates fundamental metabolic functions and is disrupted in diseases like ageing, obesity, and neurodegenerative disorders. Our final goal is the understanding of the link between altered autophagy and disease to pave the way for effective treatments. Particularly, we aim to study the relationship between autophagy and lipid metabolism. We have learnt how physiological adaptations, like lipophagy (selective degradation of lipids by autophagy) can provide energy and favor survival, preventing disease (DOI:

In our current main project, we are focusing on macrophage differentiation (M1 and M2) and how lipophagy modulates these changes. M1 macrophages are pro-inflammatory and, in many diseases, considered hurtful but M2 are anti-inflammatory and present beneficial properties. The metabolic phenotype and cytokine profile in both types of activation are quite well known. However, the molecular process that triggers the switch remains obscure. We are providing novel insights to unravel the required molecular and cellular changes to switch from M1 to M2 macrophages. Our project will point to novel targets to modulate immune activation, providing the basis for treatments for alcoholic steatohepatitis and other diseases such as non-alcoholic fatty liver, fibrosis, cirrhosis, and obesity.

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Working model. Boosting lipophagy will switch macrophages from M1 to M2 phenotype fostering an anti-inflammatory environment and ameliorating the etiopathology of alcoholic steatohepatitis (ASH).

Our group counts with great experience in the autophagy and lipophagy fields (; and knowledge of different research models, including in vitro, ex vivo, in vivo (e.g. mice, hamster, zebrafish, flies…)

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Miembros del grupo

Marina García Macia Ramón y Cajal Researcher
Adrián Santos Ledo Assistant Professor (USAL)


Marina Garcia Macia
Laboratorio 2.7

Publicaciones recientes

Brenda Morant-Ferrando*, Daniel Jimenez-Blasco*, Paula Alonso-Batan, Jesús Agulla, Rebeca Lapresa, Dario Garcia-Rodriguez, Sara Yunta-Sanchez, Irene Lopez-Fabuel, Emilio Fernandez, Peter Carmeliet, Angeles Almeida#, Marina Garcia-Macia# and Juan P. Bolaños# (2023)
Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition
Nat Metab doi: 10.1038/s42255-023-00835-6.
Lopez-Fabuel I*#, Garcia-Macia M*, Costantina Buondelmonte, Olga Burmistrova, Nicolo Bonora, Brenda Morant-Ferrando, Paula Alonso-Batan, Carlos Vicente-Gutierrez, Daniel Jimenez-Blasco, Ruben Quintana-Cabrera, 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. #.(2022)
Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis
Nat Commun 13(1):536 doi: 10.1038/s41467-022-28191-1.
Garcia‐Macia M#, Bolaños JP. (2021)
Dissecting a neuron‐to‐liver crosstalk to modulate lipid metabolism in lisosomal storage diseases
Alzheimer’s & Dementia 17, e058600 doi: 10.1002/alz.058600.
García-Macia M#, Santos-Ledo A, Leslie J, Paish HL, Collins AL, Scott RS, Watson A, Burgoyne RA, White S, French J, Hammond J, Borthwick LA, Mann J, Bolaños JP, Korolchuk VI, Oakley F, , Mann D#. (2021)
A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis
Hepatology doi: 10.1002/hep.32048.
Santos-Ledo, A.; Luxán-Delgado, B.d.; Caballero, B.; Potes, Y.; Rodríguez-González, S.; Boga, J.A.; Coto-Montes, A*; García-Macia, M*. (2021)
Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model
Antioxidants 10, 796 doi: 10.3390/antiox10050796.
Leslie J#, Garcia-Macia M, et al., F. Oakley # (2020)
c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis
Nat Metab 2, 1350–1367 doi: 10.1038/s42255-020-00306-2.

Proyectos de investigación

MCINN PID2022-138478OA-I00
Proyecto Internacionalización del IBFG de la Junta de Castilla y León CL-EI-2021-08
ESCI exploratory grant. Project entitled: “Isocaloric twice-a-day (ITAD) feeding improves brain aging” ESCI22/001, European Society for Clinical Investigation (ESCI)
Activación de la autofagia como terapia para enfermedades de almacenamiento lisosomal: enfermedad e Batten FERP21/003, Fundación Eugenio Rodríguez Pascual–Convocatoria de ayudas de investigación Biomédica 2021
Caracterización del metabolismo en la enfermedad de Batten para la búsqueda de dianas moleculares terapéuticas BH182173, Fundación Francisco Cobos. Beca Eduardo Gallego 2021.
Research Funding Support from Newcastle University C0245R4032 & C0120R3166