Personal tools
You are here: Home / Events / Seminars / [AVX Seminar] On the diversity of links between transport and metabolism of carboxylic acids | Margarida Casal

[AVX Seminar] On the diversity of links between transport and metabolism of carboxylic acids | Margarida Casal

Filed under: ,

Margarida Casal, Universidade do Minho

When 23 Feb, 2017 from
11:00 am to 12:00 pm
Where Auditorium
Add event to your calendar iCal

AVX Seminar

Title: On the diversity of links between transport and metabolism of carboxylic acids

Speaker: Margarida Casal

Affiliation: CBMA, Centre of Molecular and Environmental Biology, Department of Biology, School of Sciences, University of Minho, Braga, Portugal. mcasal@bio.uminho.pt

 

Abstract:

Carboxylic acid transporters form a heterogeneous group of proteins from different families and biological origins, showing diverse mechanisms of action and regulation. Detailed understanding of the metabolism and mechanisms of transport of these compounds has become more important than ever, both from a fundamental and from an applied point of view. In this presentation I will report distinct studies carried out in yeast, bacteria and human cells that culminated in the identification of multiple physiological roles played by lactic acid transporters (1). From a biotechnological perspective, the increasing economic value of carboxylic acid has boosted this field of research considerably. In our laboratory we manipulated the metabolism of Saccharomyces cerevisiae to produce lactic acid, demonstrating how carboxylate transporters act as modulators of carboxylic acid production and may well be used to manipulate its export in yeast cells (2). The transport of lactic acid in human cells has also gained interest for its major role in cancer cells. Most malignant tumors exhibit the Warburg effect, which manifests itself by  increased glycolysis rates with production of lactate, even in the presence of oxygen. Monocarboxylate transporters (MCTs) maintain these glycolytic rates, by mediating the influx and/or efflux of lactate and are overexpressed in several cancer cell types. In human cells MCT1-MCT4 are proton symporters, which mediate the plasma membrane transport of pyruvate, lactate and ketone bodies (3). The lactate analogue 3-bromopyruvate, an inhibitor of energy metabolism, has been proposed as a specific anti-tumor agent (4). We will discuss how yeast biology has contributed to highlight the putative role of MCTs on the anti-tumor effect of 3-bromopyruvate in breast cancer cells (5,6).

Margarida Casal
CBMA, Centre of Molecular and Environmental Biology, Department of Biology, School of Sciences, University of Minho, Braga, Portugal. mcasal@bio.uminho.pt

 
1. Casal, M., Paiva, S., Queirós, O., Soares-Silva, I. 2008. Transport of carboxylic acids in yeasts. FEMS Microbiology Reviews. 32, 974–994.
2. Ribas,D., Sa-Pessoa, J., Soares-Silva, I., Paiva, S., Nygard, Y., Ruohonen, L., Penttilä, M., Casal, M. 2017. Yeast as a tool to express sugar acid transporters with biotechnological interest FEMS Yeast Research 2017; doi: 10.1093/femsyr/fox005
3. Pinheiro, C., Longatto-Filho, A., Azevedo-Silva, J., Casal, M., Schmitt, F.C., Baltazar, F. 2012. Role of monocarboxylate transporters in human cancers: state of the art (mini-review). Journal of Bioenergetics and Biomembranes 44, 127-39.
4. Azevedo-Silva J, Queirós O, Baltazar F, Ulaszewski S, Goffeau A, Ko Y H, Pedersen P L, Preto A, Casal M. 2016. The Anticancer Agent 3-Bromopyruvate: A Simple But Powerful Molecule Taken From The Lab To The Bedside. J Bioenerg Biomembrane  48, 349–362.
5. Queirós, O., Preto, A. Pacheco, A., Pinheiro, C., Azevedo-Silva, J., Moreira, R., Pedro, M., Ko, Young, Pedersen, Peter L., Baltazar, F., Casal, M. 2012. Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate. Journal of Bioenergetics and Biomembranes 44, 141-153.
6. João Azevedo-Silva, Odília Queirós, Ana Ribeiro, Fátima Baltazar, Ko H Young, Peter L Pedersen, Ana Preto and Margarida Casal. 2015. The cytotoxicity of 3-Bromopyruvate in breast cancer cells depends on extracellular pH. Biochem. J. 467, 247–258.

 

more AVX seminars

Document Actions