CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOACaptura de pantalla 2022 09 14 a las 10.27.10    

Mouse models of disease: the role of mitochondrial bioenergetics in physiopathology

Research summary:

  • Past achievements

During the past years, our research has been focused on understanding how mitochondrial energy metabolism contributes to the integration of cellular functions, leading to the onset and progression of various pathologies. Complex regulatory mechanisms enable mitochondrial metabolism to meet cellular demands, which go beyond ATP production. We have demonstrated that mitochondrial oxidative phosphorylation also plays additional roles in controlling cell immunity and inflammation (Formentini L. et al., Cell Reports, 2017, PMID: 28494869) and regulating intra- and inter-cellular oncogenic signals (Nuevo-Tapioles, C. et al., Nature Communications, 2020, PMID: 32681016). Impaired mitochondrial function also significantly affects adipose tissue and skeletal muscle lipid species and metabolism (Formentini L et al., Diabetologia, 2017, PMID: 28770317; Sanchez-Gonzalez C et al, EMBO J. 2020, PMID: 32488939). Interestingly, these metabolic disturbances impair ROS and calcium signaling, leading to profound changes in muscle structure (Sanchez-Gonzalez C et al, Cell Death and Disease 2022, PMID: 32488939), thus emerging as key hallmarks of myopathies.

  • Future plans

One of the main goals of my research line, supported by PID2019-104241RB-I00 national funding and Fundación Ramón Areces, is to further investigate mitochondrial metabolism in pathophysiology. Using two conditional and tissue-specific mouse models with impaired mitochondrial activity (dysfunctional oxidative phosphorylation mice, LowOXPHOS mice; dysfunctional fatty acid oxidation mice, LowFAO mice), my research group is elucidating how different mitochondrial dysfunctions, environmental factors, and diets impact metabolism at the cellular, tissue, and organismal levels. We aim to identify the aspects of mitochondrial activity that limit cell homeostasis and understand which products of metabolism are essential for proper organism function, as well as how cells obtain or transform them in physiological tissue environments. This knowledge is crucial for exploiting mitochondrial metabolism for therapeutic purposes.



We are defining how skeletal muscle mitochondria dysfunctions act in an autocrine, paracrine and endocrine manner to regulate tissue metabolism. Our final aim is to identify aspects of mitochondria activity that are limiting for whole-body homeostasis in different contexts.


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Civettini Linda3264648Becario Erasmus
Formentini Laura3264648lformentini(at)cbm.csic.esProfesor Contratado Doctor Universidad, GA
Salegi AnsaBeñat3264648bsalegi(at)cbm.csic.esAyudante Investigación

Relevant publications:

  • Sánchez-González C, Herrero Martín JC, Salegi Ansa B, Núñez de Arenas C, Stančič B, Pereira MP, Contreras L, Cuezva JM, Formentini L. Chronic inhibition of the mitochondrial ATP synthase in skeletal muscle triggers sarcoplasmic reticulum distress and tubular aggregates. Cell Death & Disease 2022 Jun 22;13(6):561. doi: 10.1038/s41419-022-05016-z. PMID: 35732639; PMCID: PMC9217934.

  • Sanchez-Gonzalez C., Nuevo-Tapioles C, Herrero-Martín J, Pereira MP, Cuezva JM, Formentini L* (*corresponding author). Dysfunctional muscle oxidative phosphorylation shunts BCCA catabolism onto lipogenesis in skeletal muscle. EMBO J. 2020. e103812 CLAVE: A. Impact Factor: 11,2

  • Nuevo-Tapioles C, Santacatterina F, Stamatakis K, Nuñez de Arenas C, Gomez de Cedron, M, Formentini L and Cuezva JM. Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth. Nat Comm. 2020. 11:3606. CLAVE: A. Impact Factor: 12,1

  • Formentini L*(*: corresponding author), Ryan AJ, Gálvez-Santisteban M, Carter L, Taub P, Lapek JD Jr, Gonzalez DJ, Villarreal F, Ciaraldi TP, Cuezva JM, Henry RR. Mitochondrial H+-ATP synthase in human skeletal muscle: contribution to dyslipidaemia and insulin resistance. Diabetologia. 2017 Oct;60(10):2052-2065 CLAVE: A. Impact factor: 7,5

  • Formentini L, Santacatterina F, Núñez de Arenas C, Stamatakis K, López-Martínez D, Logan A, Fresno M, Smits R, Murphy MP, Cuezva JM. Mitochondrial ROS Production Protects the Intestine from Inflammation through Functional M2 Macrophage Polarization. Cell Rep. 2017 May 9;19(6):1202-1213. CLAVE: A. Impact factor: 8.2

  • Formentini L, Pereira MP, Sánchez-Cenizo L, Santacatterina F, Lucas JJ, Navarro C, Martínez-Serrano A and Cuezva JM. In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning. EMBO J. 2014 Apr 1; 33(7):762-78. CLAVE: A. Impact factor: 10.4

  • Formentini L, Sanchez Aragó M, Sanchez-Cenizo L, Cuezva J.M. The mitochondrial ATPase Inhibitory Factor 1 (IF1) triggers a ROS-mediated retrograde pro-survival and proliferative response. Mol Cell. 2012 Mar 30;45(6):731-42.  CLAVE: A. ImpactFactor: 15.4.

Doctoral theses:

1) Cristina Nuevo Tapioles:
FPI-Reference: BES-2014-068929
Associated Project: SAF2013-41945-R, PI: J.M Cuezva
PhD-thesis: “Regulación de la OXPHOS mediada por IF1 y su papel como diana terapéutica en cáncer”.
Thesis Defense: April 26th, 2019, UAM. Sobresaliente “cum laude”.
PhD director: Laura Formentini and J.M Cuezva

2) Cristina Sanchez Gonzalez:
FPI-Reference: BES-2017-079909
Associated Project: SAF2016-76028-R, PI: Laura Formentini
PhD-Thesis: “Papel de la bioenergética mitocondrial sobre el metabolismo del músculo esquelético durante el ejercicio y en patología “.
Thesis Defense: February 8th, 2022, UAM. Sobresaliente “cum laude”.
PhD director: Laura Formentini

3) Juan Cruz Herrero Martín (direction)
Contract funded by PID2019-104241RB-I00 project, PI: Laura Formentini
PhD-Thesis: “Papel de las deshidrogenasas FAD dependientes en la fisiopatología del musculo esquelético”
Thesis Defense: July 6th, 2022, UAM. Sobresaliente “cum laude”.
PhD director: Laura Formentini

4) Beñat Salegi Ansa (direction)
Contract funded by PID2019-104241RB-I00 project, PI: Laura Formentini
In progress.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand


What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: