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Anna Wredenberg Group

Metabolism is the complex network of chemical transformations within a living cell, required to sustain its viability. Mitochondria play a central role within most eukaryotic cells, by combining many different metabolic pathways, such as glucose and lipid metabolism, steroid and haem synthesis or apoptosis and calcium buffering. The Wredenberg group is interested in how mitochondrial dysfunction effects the rest of the cell, with a specific focus on energy metabolism.

Mitochondria are an organelle network within the majority of eukaryotic cells that undergo dynamic and complex changes of motility, shape and metabolism in response to environmental stimuli and energetic requirements. Understanding these processes, their signals and molecular basis is essential in order to appreciate the defects involved in a range of inborn errors of metabolism, but also how mitochondrial function influences common diseases, such as heart disease, diabetes, cancers, neurodegeneration or autoimmune diseases.

Mitochondria contain their own genome, a small, circular DNA molecule (mtDNA), situated in multiple copies within mitochondria. The Wredenberg group is interested in understanding what regulates mitochondrial RNA turnover, and how these RNAs are targeted for degradation. We use the fruit fly, Drosophila melanogaster, as a model system to understand regulatory mechanisms of mtDNA, what regulates mitochondrial RNA metabolism, what regulates RNA processing, turnover and how mitochondrial transcription is linked to translation. For this the group either silences factors of interest by RNA interference, or by generating genetically modified fly lines. Flies are then analysed by a range of molecular biological and biochemical techniques in order to understand the molecular mechanisms at hand.

Anna Wredenberg is a clinician at the Centre for Inherited Metabolic Diseases at the Karolinska University Hospital, Stockholm, Sweden, which has specialised on rare genetic diseases involving mitochondrial dysfunction. Advances in sequencing technology has enabled us to rapidly diagnose many known inborn errors of metabolism, but has also lead to a surge in novel disease-candidates, where pathogenicity needs to be validated.

The Wredenberg group attempts to understand the molecular basis of disease formation, using primary patient cells or reprogrammed neuronal stem cells in order to investigate metabolic derangements in disease progression. Generating disease-specific fly models allows for the investigation of patient-relevant metabolic disturbances in an in vivo model.

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