Research Divisions

Autophagy and Metabolism

Group LeaderLocation and ContactMembersHistory of the GroupLines of ResearchNotable PublicationsProjectsPhD ThesesClinical TrialsNews
Dr 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 31-8-2018 (Scopus/Thomson-Reuters):

Peer-reviewed scientific articles: 61

Number of citations received: 9680

Average number of citations per article: 149

H-index: 33

orcid.org/0000-0003-1960-1677

Scopus: Author ID: 7202998423

Edificio ISPA-FINBA

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

NamePositionOrganisation
Guillermo Mariño GarcíaPrincipal Investigator
Isaac Tamargo GómezPhD Researcher with an FPU (university teacher training) grantUniversidad de Oviedo
Gemma Martínez GarcíaPhD Researcher with an FPI (research staff training) grantUniversidad de Oviedo
María Fernández SuárezLaboratory Technician
Olivia Concepción Fernández CimadevillaPostdoctoral Researcher

 

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.

  1. 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)8.032Q1 CELL BIOLOGY

 

  1. 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

 

 

  1. 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)5.168Q1 ONCOLOGY

 

 

  1. 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)1.984Q3 BIOCHEMISTRY&MOL. BIOLOGY

 

 

  1. 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)5.638Q1 CELL BIOLOGY

 

  1. 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)10.557Q1 CELL BIOLOGY

 

  1. 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)27.407Q1 CELL BIOLOGY

 

  1. 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)8.593Q1 CELL BIOLOGY

 

  1. 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)8.218Q1 CELL BIOLOGY

 

  1. 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)9.643Q1 CELL BIOLOGY

 

  1. 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)11.75Q1 CELL BIOLOGY

 

  1. 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)7.52Q1 GENETICS & HEREDITY

 

  1. 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)4.56Q2 CELL BIOLOGYCELL BIOLOGY

 

  1. 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)11.75Q1 CELL BIOLOGY

 

  1. 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)11.75Q1 CELL BIOLOGY

 

  1. 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)14.01Q1 CELL BIOLOGY

 

  1. 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)37.86Q1 CELL BIOLOGY

 

  1. 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)8.124Q1 CELL BIOLOGY

 

  1. 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)11.75Q1 CELL BIOLOGY

 

  1. 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)17.565Q1 ENDOCRINOLOGY AND METABOLISM

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: 01/01/2016 -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: 01/01/2016 - 21/02/2017