Research Divisions

Autophagy and Metabolism

Group LeaderLocation and ContactMembersHistory of the GroupLines of ResearchNotable PublicationsProjectsPhD ThesesNews
Dr Guillermo Mariño García

Guillermo Mariño García

The research career of the Autophagy and Metabolism Research Group’s principal investigator has focused on a range of factors relating to autophagy since beginning his PhD thesis at the Universidad de Oviedo (under the supervision of Professor Carlos López-Otín). In 2005, he completed a productive posting at one of the most cutting-edge laboratories in the autophagy field (Dr Noboru Mizushima’s laboratory in Tokyo, Japan), which increased his interest in this process even further. Once he had submitted his PhD thesis, titled “proteinases and autophagy: an analysis of their relevance in cancer and ageing”, he completed an extended five-year postdoctoral fellowship in Professor Guido Kroemer’s laboratory in Paris, where he studied the role of autophagy in processes associated with ageing. In 2016, the “Autophagy and Metabolism” research group was officially established, whose lines of research explore autophagy from a range of perspectives.

Bibliometric data on the group’s PI as of 14-7-2022 (Scopus/Thomson-Reuters):

Peer-reviewed scientific articles: 70

Number of citations received: 18,107

Average number of citations per article: 261

H-index: 41

orcid.org/0000-0003-1960-1677

Scopus: Author ID: 7202998423

Edificio ISPA-FINBA

Avenida Hospital Universitario, s/n 33011 Oviedo, Spain.

Name Organisation Activity Euraxess classification
Fernández Cimadevilla, Oliva Concepción SESPA Research/Clinical R2
Fernández Fernández, Álvaro Universidad de Oviedo Research R2
Mariño García, Guillermo Universidad de Oviedo Research/Teaching R4
Martínez García, Gemma Universidad de Oviedo Research R1
Tamargo Gómez, Isaac Universidad de Oviedo Research R1
Fernández Suárez, María FINBA Research No classification

 

The Autophagy and Metabolism group is a new and emerging research group which has gradually taken shape since the beginning of 2015, when the principal investigator returned to Spain with the support of a Ramón y Cajal contract, after a five-year postdoctoral fellowship abroad. The Autophagy and Metabolism group’s lines of research cover a range of factors related to the autophagy process. This process is essential for maintaining cell health and tissue functions. In fact, this constant process of renewing the cell’s contents is what enables the cell to carry out its functions properly. Without it, damaged structures, dysfunctional organelles and misfolded or damaged proteins would accumulate in the cell, which would seriously and progressively impede cell functioning, thereby preventing tissues and the organism from functioning. From 2015 to mid-2016, the principal investigator’s work focused primarily on securing funding and recruiting students, so as to put in place sufficient resources for research to begin. The group’s team of researchers has been gradually expanding since then.

In summer 2016, the group was officially established as an ISPA emerging research group, performing its work in the FINBA building, where the laboratory is housed.

The organisational structure of the Autophagy and Metabolism group is currently as follows:

Dr Guillermo Mariño (PI), Group Leader, responsible for management, securing resources and communicating the results obtained.

María F. Fernández, Laboratory Technician, has been a group member since June 2016.

Gemma Martínez, (PhD Student), has been a group member since May 2017 and is an FPI grantholder. Gemma is currently working on her PhD thesis, which is being supervised by the group’s PI.

Isaac Tamargo, (PhD Student). Isaac has been a group member since December 2017 and is an FPU grantholder. He is currently working on his PhD thesis, which is being supervised by the group’s PI.

Dr Oliva Concepción Fernández Cimadevilla joined the group in January 2018.

The Autophagy and Metabolism group’s lines of research cover a range of factors related to the autophagy process. This process is essential for maintaining cell health and tissue functions. In fact, this constant process of renewing the cell’s contents is what enables the cell to carry out its functions properly. Without it, damaged structures, dysfunctional organelles and misfolded or damaged proteins would accumulate in the cell, which would seriously and progressively impede cell functioning, thereby preventing tissues and the organism from functioning.

Within this field, our research group is working on two main lines of research, both of which focus on autophagy.

The first line of research centres on the molecular characterisation of the Atg4/Atg8 families’ specific functions in the context of autophagy. The group’s principal investigator has been responsible (when completing his PhD thesis) for the cloning and functional description of the genes of human Atg4 proteinases, known as autophagins (Mariño et al JBC 2003). This system is of particular interest when studying autophagy in mammals because, while other essential genes for autophagy in simple eukaryotes (yeasts) have only one orthologue in mammals, the Atg4 yeast proteinase has four orthologues (autophagins 1-4) and its substrate (Atg8) has six orthologues in human cells (Fernández and López-Otín, J Clin Invest 2013). In fact, this constant process of renewing the cell’s contents is what enables the cell to carry out its functions properly. Without it, damaged structures, dysfunctional organelles and misfolded or damaged proteins would accumulate in the cell, which would seriously and progressively impede cell functioning, thereby preventing tissues and the organism from functioning.

Within this line of research, our group continues to generate the mouse models that are deficient in the various autophagins. Previously, the group’s PI has been responsible for the generation and characterisation of mouse models that are deficient in Atg4C or Autophagin-3, (Mariño, G et al JBC 2003) and Atg4B or Autophagin1 (Mariño G et al, J Clin Invest, 2010). Our research group has already generated an Atg4D- or Autophagin 4-deficient mouse model (Tamargo-Gómez et al, article currently under review) and has begun the generation of Atg4A-deficient animal models. In the medium term, our objective is to characterise the various functions of this family of proteinases and establish why evolutionary gene amplification has been particularly prevalent in this family of proteinases and its substrates. The possibility of generating double or triple-mutant animal models for the various combinations of proteinases is one of the main objectives of this line of research, which is certain to lead to new and interesting discoveries about the physiological functions of autophagins in the context of higher eukaryotes, particularly mammals.

As an essential, complementary part of this line of research, our group uses MEF (mouse embryonic fibroblast)-type cells generated from these animals. Studying the various molecular aspects of autophagy in these cell models (including cell lines with combinations of two or three autophagins) enables us to clearly identify the specific functions of these proteinases, and accurately determine the proteinase-substrate specificity of the Atg4/Atg8 families.

Our laboratory’s second line of research analyses the role of autophagy in a range of pathological-physiological processes: from ageing to cancer and other pathologies, paying particular attention to diabetes, obesity and cardiopathies.

For this area of research, our laboratory has several models with a reduced autophagic response (Atg4B, Mariño et al, J Clin Invest 2010), Ambra1 HT mice (Fimia GM, Nature 2007) and models with an increase in the basal levels of autophagy (Becn1F121A/F121A knock-in mice, Fernández AF et al, Nature 2018). The coordinated application of experimental protocols in these mouse models will enable us to establish whether autophagy plays a beneficial or harmful role in a certain pathophysiological process. A recent publication (Fernández AF et al. Cell Death Dis 2017) in which we analyse the anti-obesity role of the process provides an example of this strategy, as does a 2013 publication demonstrating that autophagy plays an essential role against chronic ulcerative colitis, of which the group’s PI is co-lead author (Cabrera et al, Autophagy 2013). One of themain elements of this experimental line of research involves performing calorific-restriction protocols on autophagin-1-deficient mice. The ultimate objective of this project is to gain more in-depth knowledge on the role which, according to the existing literature, autophagy is very likely to play in extending longevity.

 

  • Ignacio Ramírez-Pardo, Beatriz Villarejo-Zori, Juan Ignacio Jiménez-Loygorri, Elena Sierra-Filardi, Sandra Alonso-Gil, Guillermo Mariño, Pedro de la Villa, Patrick S Fitze, José Manuel Fuentes, Ramón García-Escudero, Raquel Gomez-Sintes, Patricia Boya. Ambra1 haploinsufficiency results in metabolic alterations and exacerbates age-associated retinal degeneration. Autophagy. 2022 In Press.
Impact factor (SCI/SSCI) 16.016 D1 CELL BIOLOGY
  • Martínez-García GG, Pérez RF, Fernández ÁF, Durand S, Kroemer G, Mariño G. Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice. Metabolites. 2021 Jul 27;11(8):481. doi: 10.3390/metabo11080481.
Impact factor (SCI/SSCI) 4.932 Q2 BIOCHEMISTRY&MOL. BIOLOGY
  • Tamargo-Gómez I, Martínez-García GG, Suárez MF, Fernández AF, Mariño G. ATG4D role in mAtg8s delipidation and neuroprotection. Autophagy. 2021 Jun;17(6):1558-1560. doi: 10.1080/15548627.2021.1922979
Impact factor (SCI/SSCI) 16.016 D1 CELL BIOLOGY
  • Tamargo-Gómez I, Martínez-García GG, Suárez MF, Rey V, Fueyo A, Codina-Martínez H, Bretones G, Caravia XM, Morel E, Dupont N, Cabo R, Tomás-Zapico C, Souquere S, Pierron G, Codogno P, López-Otín C, Fernández ÁF, Mariño G. ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration. Cell Death Differ. 2021 Sep;28(9):2651-2672. doi: 10.1038/s41418-021-00776-1.
Impact factor (SCI/SSCI) 15.828 D1  BIOCHEMISTRY&MOL. BIOLOGY
  • Klionsky DJ and multiple authors (including Mariño G.). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280.
Impact factor (SCI/SSCI) 16.016 D1 CELL BIOLOGY
  • Tamargo-Gómez I, Fernández ÁF, Mariño G. Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes. Int J Mol Sci. 2020 Nov 2;21(21):8196. doi: 10.3390/ijms21218196.
Impact factor (SCI/SSCI) 5.924 Q1  BIOCHEMISTRY&MOL. BIOLOGY
  • Martínez-García GG, Mariño G. Autophagy role in environmental pollutants exposure. Prog Mol Biol Transl Sci. 2020;172:257-291. doi: 10.1016/bs.pmbts.2020.02.003.
Impact factor (SCI/SSCI) 3.622 Q3  BIOCHEMISTRY&MOL. BIOLOGY
  • De Marañon AM, Iannantuoni F, Abad-Jiménez Z, Canet F, Díaz-Pozo P, López-Domènech S, Jover A, Morillas C, Mariño G, Apostolova N, Rocha M, Victor VM. Relationship between PMN-endothelium interactions, ROS production and Beclin-1 in type 2 diabetes. Redox Biol. 2020 Jul;34:101563. doi: 10.1016/j.redox.2020.101563.
Impact factor (SCI/SSCI) 11.799 D1  BIOCHEMISTRY&MOL. BIOLOGY
  • Tamargo-Gómez I, Mariño G. AMPK: Regulation of Metabolic Dynamics in the Context of Autophagy. Int J Mol Sci. 2018 Nov 29;19(12):3812. doi: 10.3390/ijms19123812.
Impact factor (SCI/SSCI) 5.924 Q1  BIOCHEMISTRY&MOL. BIOLOGY
  • Barcena C, Quiros PM, Durand S, Mayoral P, Rodriguez F, Caravia XM, Marino G, Garabaya C, Fernandez-Garcia MT, Kroemer G, Freije JMP, Lopez-Otin C. Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism. Cell reports 2018, 24(9): 2392-2403.
Impact factor (SCI/SSCI) 8.032 Q1 CELL BIOLOGY
  • Pietrocola F, Castoldi F, Markaki M, Lachkar S, Chen G, Enot DP, Durand S, Bossut N, Tong M, Malik SA, Loos F, Dupont N, Marino G, Abdelkader N, Madeo F, Maiuri MC, Kroemer R, Codogno P, Sadoshima J, et al. Aspirin Recapitulates Features of Caloric Restriction. Cell reports 2018, 22(9): 2395-2407.
Impact factor (SCI/SSCI) 8.032 (SCI/SSCI) Q1 CELL BIOLOGY
  • Sica V, Bravo-San Pedro JM, Chen G, Marino G, Lachkar S, Izzo V, Maiuri MC, Niso-Santano M, Kroemer G. Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget 2017, 8(52): 89527-89538.
Impact factor (SCI/SSCI) 5.168 Q1 ONCOLOGY
  • Lopez-Otin C, Marino G. Tagged ATG8-Coding Constructs for the In Vitro and In Vivo Assessment of ATG4 Activity. Methods in enzymology 2017, 587: 189-205.
Impact factor (SCI/SSCI) 1.984 Q3 BIOCHEMISTRY&MOL. BIOLOGY
  • Fernandez AF, Barcena C, Martinez-Garcia GG, Tamargo-Gomez I, Suarez MF, Pietrocola F, Castoldi F, Esteban L, Sierra-Filardi E, Boya P, Lopez-Otin C, Kroemer G, Marino G. Autophagy couteracts weight gain, lipotoxicity and pancreatic beta-cell death upon hypercaloric pro-diabetic regimens. Cell death & disease 2017, 8(8): e2970.
Impact factor (SCI/SSCI) 5.638 Q1 CELL BIOLOGY
  • Esteban-Martinez L, Sierra-Filardi E, McGreal RS, Salazar-Roa M, Marino G, Seco E, Durand S, Enot D, Grana O, Malumbres M, Cvekl A, Cuervo AM, Kroemer G, Boya P. Programmed mitophagy is essential for the glycolytic switch during cell differentiation. The EMBO journal 2017, 36(12): 1688-1706.
Impact factor (SCI/SSCI) 10.557 Q1 CELL BIOLOGY
  • Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, et al. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer cell 2016, 30(1): 147-160.
Impact factor (SCI/SSCI) 27.407 Q1 CELL BIOLOGY
  • Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 2016, 12(1): 1-222.
Impact factor (SCI/SSCI) 8.593 Q1 CELL BIOLOGY
  • Pietrocola F, Lachkar S, Enot DP, Niso-Santano M, Bravo-San Pedro JM, Sica V, Izzo V, Maiuri MC, Madeo F, Marino G, Kroemer G. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell death and differentiation 2015, 22(3): 509-516.
Impact factor (SCI/SSCI) 8.218 Q1 CELL BIOLOGY
  • Niso-Santano M, Malik SA, Pietrocola F, Bravo-San Pedro JM, Marino G, Cianfanelli V, Ben-Younes A, Troncoso R, Markaki M, Sica V, Izzo V, Chaba K, Bauvy C, Dupont N, Kepp O, Rockenfeller P, Wolinski H, Madeo F, Lavandero S, et al. Unsaturated fatty acids induce non-canonical autophagy. The EMBO journal 2015, 34(8): 1025-1041.
Impact factor (SCI/SSCI) 9.643 Q1 CELL BIOLOGY
  • Schroeder S, Pendl T, Zimmermann A, Eisenberg T, Carmona-Gutierrez D, Ruckenstuhl C, Marino G, Pietrocola F, Harger A, Magnes C, Sinner F, Pieber TR, Dengjel J, Sigrist SJ, Kroemer G, Madeo F. Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity. Autophagy 2014, 10(7): 1335-1337.
Impact factor (SCI/SSCI) 11.75 Q1 CELL BIOLOGY
  • Ruckenstuhl C, Netzberger C, Entfellner I, Carmona-Gutierrez D, Kickenweiz T, Stekovic S, Gleixner C, Schmid C, Klug L, Sorgo AG, Eisenberg T, Buttner S, Marino G, Koziel R, Jansen-Durr P, Frohlich KU, Kroemer G, Madeo F. Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification. PLoS genetics 2014, 10(5): e1004347.
Impact factor (SCI/SSCI) 7.52 Q1 GENETICS & HEREDITY
  • Pietrocola F, Malik SA, Marino G, Vacchelli E, Senovilla L, Chaba K, Niso-Santano M, Maiuri MC, Madeo F, Kroemer G. Coffee induces autophagy in vivo. Cell cycle 2014, 13(12): 1987-1994.
Impact factor (SCI/SSCI) 4.56 Q2 CELL BIOLOGYCELL BIOLOGY
  • Marino G, Pietrocola F, Madeo F, Kroemer G. Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers. Autophagy 2014, 10(11): 1879-1882.
Impact factor (SCI/SSCI) 11.75 Q1 CELL BIOLOGY
  • Marino G, Pietrocola F, Kong Y, Eisenberg T, Hill JA, Madeo F, Kroemer G. Dimethyl alpha-ketoglutarate inhibits maladaptive autophagy in pressure overload-induced cardiomyopathy. Autophagy 2014, 10(5): 930-932.
Impact factor (SCI/SSCI) 11.75 Q1 CELL BIOLOGY
  • Marino G, Pietrocola F, Eisenberg T, Kong Y, Malik SA, Andryushkova A, Schroeder S, Pendl T, Harger A, Niso-Santano M, Zamzami N, Scoazec M, Durand S, Enot DP, Fernandez AF, Martins I, Kepp O, Senovilla L, Bauvy C, et al. Regulation of autophagy by cytosolic acetyl-coenzyme A. Molecular cell 2014, 53(5): 710-725.
Impact factor (SCI/SSCI) 14.01 Q1 CELL BIOLOGY
  • Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nature reviews Molecular cell biology 2014, 15(2): 81-94.
Impact factor (SCI/SSCI) 37.86 Q1 CELL BIOLOGY
  • Ko A, Kanehisa A, Martins I, Senovilla L, Chargari C, Dugue D, Marino G, Kepp O, Michaud M, Perfettini JL, Kroemer G, Deutsch E. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell death and differentiation 2014, 21(1): 92-99.
Impact factor (SCI/SSCI) 8.124 Q1 CELL BIOLOGY
  • Eisenberg T, Schroeder S, Buttner S, Carmona-Gutierrez D, Pendl T, Andryushkova A, Marino G, Pietrocola F, Harger A, Zimmermann A, Magnes C, Sinner F, Sedej S, Pieber TR, Dengjel J, Sigrist S, Kroemer G, Madeo F. A histone point mutation that switches on autophagy. Autophagy 2014, 10(6): 1143-1145.
Impact factor (SCI/SSCI) 11.75 Q1 CELL BIOLOGY
  • Eisenberg T, Schroeder S, Andryushkova A, Pendl T, Kuttner V, Bhukel A, Marino G, Pietrocola F, Harger A, Zimmermann A, Moustafa T, Sprenger A, Jany E, Buttner S, Carmona-Gutierrez D, Ruckenstuhl C, Ring J, Reichelt W, Schimmel K, et al. Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan. Cell metabolism 2014, 19(3): 431-444.
Impact factor (SCI/SSCI) 17.565 Q1 ENDOCRINOLOGY AND METABOLISM

Analysis of autophagy functions in aging through the study of ATG4 proteases-deficient models

  • Lead Researcher: Guillermo Mariño
  • Other Participating Group Members: Gemma Martínez García
  • Funding Body: Ministerio de Ciencia e Innovación
  • Reference Number: PID2021-127534OB-I00
  • Funding Awarded: 187.550 €
  • Duration: 1/9/2022 -31/8/2025

Grants to support the activity of research groups in the Principality of Asturias

  • Investigador responsable: Guillermo Mariño
  • Funding Body: Gobierno del Principado de Asturias
  • Reference Number: IDI2018/159
  • Funding Awarded: 90.200 €
  • Duration: 1/1/2020 -31/12/2020

Molecular characterisation of the independent and dependent autophagy mechanisms involved in the extension of longevity

  • Lead Researcher: Guillermo Mariño
  • Other Participating Group Members: Gemma Martínez García
  • Funding Body: Ministerio de Economía y Competitividad
  • Reference Number: BFU2015-68539-R
  • Funding Awarded: €160,000
  • Duration: 1/1/2016 -31/12/2019

Breaking down autophagy nutritional regulation to molecular level

  • Lead Researcher: Guillermo Mariño
  • Funding Body: Fundación BBVA
  • Reference Number: BBM_BIO_3015
  • Funding Awarded: €40,000
  • Duration: 1/1/2016 – 21/2/2017
  • Gemma Martínez García: “Role of the ATG4 proteases in the tight relationship between autophagy and longevity”. Universidad de Oviedo (2021). Summa cum laude.
  • Álvaro Fernández Fernández: “Análisis Funcional y Patológico de Proteasas Involucradas en Autofagia” (codirector, Carlos López Otín). Universidad de Oviedo (2015). Summa cum laude, European Honours, Outstanding PhD thesis award.
  • Federico Pietrocola: “Autophagy regulation by calorie restriction mimetics, relevance in longevity and cancer treatment” (codirector, Guido Kroemer). Université Paris-Descartes, París, Francia (2015). Summa cum laude, European Honours, Outstanding PhD thesis award.