Integration of cell signaling and cellular metabolism

Research summary:

The brain has a very high metabolic demand, and compelling evidence over the last years has evidenced that the source of energy that neurons and glial cells utilize contributes to shape neuronal function and survival. However, little is known on how brain cells adapt to changes in metabolic situations, such as “energy fuel” availability and other extracellular cues. Furthermore, how the utilization of select fuels contribute to modulate neuronal excitability and survival remains poorly understood.

Our current research focuses on understanding how signaling cascades regulate energy metabolism in the brain, with a special focus on mitochondria. Mitochondrial metabolism plays a key role in cellular physiology, which is underscored by the fact that mitochondrial dysfunction and metabolic decline have been linked to several neurological disorders. Our previous studies have shown that manipulation of the metabolic program in the brain constitutes a promising therapeutic strategy to treat disorders in which metabolic dysfunction is a central feature. Therefore, understanding the molecular mechanisms that modulate energy metabolism and mitochondrial function will contribute to gain insight into the underpinnings responsible for the pathogenesis of such diseases.

In particular, we are interested in:

  1. Identification and characterization of signaling mechanisms that regulate the choice of fuel in brain cells.

  2. Study the molecular underpinnings that link metabolic flow with neuronal function and viability.

  3. Ultimately, we plan to utilize this knowledge to design and evaluate potential therapeutic strategies against mitochondrial dysfunction-induced neurological disorders.

To address these questions, we use a multidisciplinary approach that combines cellular biology, metabolic flux analysis, biochemistry, proteomics, molecular biology and in vivo studies. Our ultimate goal is to identify integrative mechanisms of regulation of energy metabolism and to develop novel therapeutic strategies for neurological disorders in which aberrations in metabolism play a prominent role. In this regard, we conduct part of our research in close collaboration with the group of Dr. Javier Díaz Nido.

Image

Nutrients and other metabolic clues impinge on neurons and crosstalk with signaling networks to modulate function and survival.

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Giménez Cassina SendonAlfredo2074594agcassina(at)cbm.csic.esInvestigador

Relevant publications:

  • Katsu-Jiménez Y, Giménez-Cassina A, “Fibroblast Growth Factor-21 promotes ketone body utilization in neurons through AMP-dependent kinase activation” Mol Cell Neurosci, In press
  • Katsu-Jimenez Y, Vázquez-Calvo C, Maffezzini C, Halldin M, Peng X, Freyer C, Wredenberg A, *Giménez-Cassina A, *Wedell A, *Arnér ESJ, “Absence of TXNIP in humans leads to lactic acidosis and low serum methionine linked to deficient respiration on pyruvate, Diabetes, 2019, 68(4):709-723 (* AGC, AW & ESJ: Co-senior authors)
  • Femenía T, Giménez-Cassina A, Codeluppi S, Fernández-Zafra T, Katsu-Jiménez Y, Terrando N, Eriksson LI, Gómez-Galán M. "Disrupted neuro-glial metabolic coupling after peripheral surgery", Journal of Neuroscience, 2018, 38(2):452-464
  • Katsu-Jiménez Y, Alves RM, Giménez-Cassina A, "Food for thought: Impact of metabolism on neuronal excitability", Experimental Cell Research, 2017, 360(1):41-416
  • Peng X., Giménez-Cassina A, Petrus P, Conrad M, Rydén M, Arnér ES, "Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness". Scientific Reports, 2016, 6:28080
  • *Gimenez-Cassina A, Danial NN, “Regulation of mitochondrial nutrient and energy metabolism by BCL-2 proteins”, Trends in Endocrinology and Metabolism, 2015, 26(4):165-175 (*AGC: Corresponding author)
  • Gimenez-Cassina A, Garcia-Haro L, Choi CS, Osundiji MA, Lane EA, Huang H, Yildirim MA, Szlyk B, Fisher JK, Polak K, Patton E, Wiwczar J, Robertson K, Godes M, Kim S, Kulkarni A, Distefano A, Samuel V, Cline G, Kim YB, Shulman GI, Danial NN, “Regulation of hepatic energy metabolism and gluconeogenesis by BAD”, Cell Metabolism, 2014, 19:272-284
  • Gimenez-Cassina A, Martinez-François JR, Fisher JK, Szlyk B, Polak K, Wiwczar J, Tanner GF, Lutas A, Yellen G, Danial NN, "BAD-Dependent regulation of fuel metabolism and KATP channel activity confers resistance to epileptic seizures", Neuron, 2012, 74(4):719-730
  • Gimenez-Cassina A, Wade-Martins R, Gomez-Sebastian S, Corona JC, Lim F, Diaz-Nido J, “Infectious delivery and long-term persistence of transgene expression in vivo by a 135 kb iBAC-FXN genomic DNA expression vector”, Gene Therapy, 2011, 18(10):1015-1019
  • Gimenez-Cassina A, Danial NN. “Noxa: A Sweet Twist to Survival and More”, Molecular Cell, 2010, 40(5):687-688
  • Gimenez-Cassina A, Lim F, Cerrato T, Palomo GM, Diaz-Nido J. “Mitochondrial Hexokinase II promotes neuronal survival and acts downstream of glycogen synthase kinase-3”. Journal of Biological Chemistry, 2009, 284(5):3001-3011

Doctoral theses:

  • Mauro Agrò (July 2019; Universidad Autónoma de Madrid; Co-supervisor. Main supervisor: Dr. Javier Díaz Nido)
  • Ana Canerina Luis Amaro (expected: January 2020; Universidad de La Laguna; Co-supervisor. Main supervisor: Dr. Raquel Marín Cruzado)

NOTE! This site uses cookies and similar technologies.

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

I understand

COOKIES POLICY

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: