Drosophila metabolism research group
- 1. Mitochondrion is best known as the major site of ATP synthesis, but it is also involved in many other metabolic processes, e.g. synthesizing a number of metabolites that are important for various cellular processes. Vast majority of proteins that carry out these functions are transported from cytosol, since only a small part (13 proteins) of the mitochondrial proteome is synthesized within this organelle. However, these 13 proteins are vital parts of electron transport chain (ETC) complexes. This system creates a proton gradient for ATP synthesis, also generating a mitochondrial membrane potential which is required for the transport of proteins into the mitochondria. These 13 proteins are encoded by mitochondrial DNA (mtDNA), a remnant of the genome of a mitochondrial free-living ancestor. Therefore all mitochondrial processes depend on the normal maintenance of mtDNA. Disorders in integrity and/or function of mtDNA cause severe, often fatal, pathologies in humans. The topic of my research is to find out how mtDNA synthesis and transcription are coordinated and to what extent are these two processes intertwined. As a result of my work, I have discovered that a tight regulation of DNA and RNA synthesis is necessary to avoid their collisions on the mtDNA template. When this occurs, both processes are disrupted, with severe downstream effects on survival and metabolism in the Drosophila model organism. Moreover, transcription also supports DNA synthesis, as replication can only proceed if the RNA strand generated by transcription hybridizes with the lagging DNA strand, providing RNA primers for the synthesis of that strand.
2. Similar to nuclear chromatin, mitochondrial DNA exists in DNA-protein complex termed mitochondrial nucleoid. Many of these proteins are directly involved in DNA synthesis and gene expression - DNA and RNA polymerases, transcription factors, helicase etc. However, numerous enzymes have been identified in nucleoids that play a central role in important metabolic pathways. It is therefore possible that the stability of mtDNA and its in vivo context may also affect metabolism directly, not only through ETC. So far, however, there is only circumstantial evidence of such connections. I have constructed a mechanism based on the bacterial endonuclease EcoBI that is capable of influencing mtDNA in vivo in a Drosophila. As a result, I have discovered a novel link between mtDNA and general metabolism, where disturbances in mtDNA stability lead to an inability to consume carbohydrates and reorient metabolism towards lipid oxidation. This is caused by two phenomena - both glucose transport into the cell and subsequent catabolism by glycolysis are inhibited. These changes are very similar to the processes that cause type I diabetes in humans, therefore my discovery on this role of mtDNA provides novel insight to the onset of this metabolic pathology.
3. In addition to the research topics listed above, I also investigate the effects of stress due to changing environmental conditions on the overall metabolism of Drosophila and other insects. These stress conditions can be either naturally occurring (e.g. anthropogenic changes in the environment) or induced in laboratory conditions. As an example of the latter, I and my collaborators have found that predator stress causes significant changes in both brain-specific and general, systemic metabolism of fruit flies. These results, which have not yet been published, suggest causal relationships between psychological stress conditions and environmental conditions that and changes causing pathologies.
- Popovs, Sergejs; Munkevics, Maris; Krama, Tatjana; Krams, Ronalds, Sledevskis, Erics; Trakimas, Giedrius; Zants, Krists; Grigorjeva, Tatjana; Mizers, Valdis; Kolbjonoks, Vadims; Jõers, Priit; Krams, Indrikis. (2024). Explaining the survival of the sickest: altered walking patterns are linked with improved adult survival in Drosophila melanogaster grown with predators during larval development. Behaviour, 1−16. DOI: 10.1163/1568539X-bja10254
- Krama, Tatjana & Bahhir, Diana & Ots, Liina & Popovs, Sergejs & Bartkevics, V. & Pugajeva, Iveta & Krams, Ronalds & Merivee, Enno & Must, Anne & Rantala, Markus & Krams, Indrikis & Jõers, Priit. (2023). A diabetes-like biochemical and behavioural phenotype of Drosophila induced by predator stress. Proceedings of the Royal Society B. 290. https://doi.org/10.1098/rspb.2023.0442
- Krama, T., Munkevics, M., Krams, R., Grigorjeva, T., Trakimas, G., Jõers, P., Popovs, S., Zants, K., Elferts, D., Rantala, M. J., Sledevskis, E., Contreras-Garduño, J., de Bivort, B. L., & Krams, I. A. (2023). Development under predation risk increases serotonin-signaling, variability of turning behavior and survival in adult fruit flies Drosophila melanogaster. Frontiers in behavioral neuroscience, 17, DOI: 10.3389/fnbeh.2023.1189301
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