Laboratory of Bioenergetics

Obesity, high blood sugar levels, and insulin resistance are among the most common symptoms of metabolic syndrome. However, its hereditary causes are not yet fully understood. Scientists from the Laboratory of Bioenergetics of the Institute of Physiology of the Czech Academy of Sciences and the CarDia National Institute have discovered that DNA variability in mitochondria could play an important role in the development of metabolic syndrome symptoms.

Press release (in Czech)

Reference: Pecina P., Čunátová K., Kaplanová V., Puertas-Frias G., Šilhavý J., Tauchmannová K., Vrbacký M., Čajka T., Gahura O., Hlaváčková M., Stránecký V., Kmoch S., Pravenec M., Houštěk J., Mráček T., Pecinová A.: Haplotype variability in mitochondrial rRNA predisposes to metabolic syndrome. Communications Biology 7(1):1116 (2024). DOI

Animal models of human mitochondrial diseases enable detailed insight into pathogenic mechanisms, from molecular to organismal levels. More

Inborn disorders of energy provision by mitochondrial respiratory chain are the primary cause of numerous serious diseases, ranging from most severe encephalo-cardio-myopathies manifesting early after birth to various tissues-specific and milder disorders affecting mainly adults. More

One important paradigm of mitochondrial ROS production modulation states that high levels of mitochondrial membrane potential (ΔΨ_m) increase ROS generation in the respiratory chain. In a common project with the laboratory of Prof Cannon (The Wenner-Gren Institute, Stockholm, Sweden), we addressed this hypothesis on a model of brown adipose tissue (BAT) mitochondria, where ΔΨ_m is dissipated by the action of uncoupling protein 1 (UCP1). We compared the ROS production in BAT mitochondria isolated from wild-type mice or from UCP1−/− mice (with a high membrane potential) and found only ROS production supported by exogenously added succinate was affected by the presence of active UCP1. ROS production supported by any other tested substrate (including endogenously generated succinate) was not affected by ΔΨ_m. This indicates that UCP1 is not involved in the control of ROS production in BAT mitochondria, possibly indicating that also under other situations membrane depolarisation would not decrease physiologically relevant ROS production (Shabalina et al., Biochim Biophys Acta 1837: 2017, 2014)

Biophys Acta 1837: 2017, 2014

We don’t know the detailed mechanism of ROS production for the majority of enzymes that have been shown to generate ROS. However, a known mechanism of this process is an essential prerequisite for searching for potential therapeutic compounds.  We have recently shed light on the mechanism of ROS production by one of these enzymes – mitochondrial glycerol-3-phosphate dehydrogenase. You can read the paper in BBA Bioenergetics.

Tomáš Mráček, Eliška Holzerová, Zdeněk Drahota, Nikola Kovářová, Marek Vrbacký, Pavel Ješina, Josef Houštěk: ROS generation and multiple forms of mammalian mitochondrial glycerol-3-phosphate dehydrogenase

Mitochondrial glycerol-3-phosphate dehydrogenase

Is an important enzyme at the crossroads of glucose metabolism, lipid metabolism and mitochondrial oxidative phosphorylation. It represents one of the pathways, how to transport reducing equivalents from cytosol into mitochondria. In this so called glycerophosphate shuttle mGPDH has its cytosolic partner – cGPDH. In many cell types, glycerophosphate shuttle is only secondary to the better known malate/aspartate shuttle, which also transfers reducing equivalents to mitochondria.