The mitochondrion is a key player in cellular function and dysfunctional mitochondria have been implicated in a number of disorders as well as in the process of normal ageing. Our research group is interested in fundamental questions related to mitochondrial biology. How is the number and the function of mitochondria regulated? What happens in a cell with dysfunctional mitochondria? How does mitochondrial dysfunction cause human disease?
Photo: Nils-Göran Larssons labbA new study published in Cell Metabolism by the research group of Professor Nils-Göran Larsson, at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, shows that so-called supercomplexes have no major role in cellular energy production and that altered levels therefore are unlikely to affect physiology and disease.
Photo: N/AJelena Misic, PhD in Nils-Göran Larsson Group at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, has been selected to participate in the Lindau Nobel Laureate Meetings in June 2023. Jelena studies different aspects of mitochondrial gene expression in mammals.
Professor Nils-Göran Larsson receives a Novo Nordisk Foundation Project Grant of DKK 3 million. Roberta Filograna receives a grant from the Åhlén foundation.
Photo: Getty ImagesA recent study in Science Advances by the group, in cooperation with Max Planck Institute, shows that neurons can counteract degeneration and promote survival by adapting their metabolism. It challenges the long-standing view that neurons cannot adjust their metabolism and therefore irreversibly degenerate. These findings may contribute to developing therapeutic approaches for patients with mitochondrial diseases and other types of neurodegeneration, such as Parkinson’s Disease.
Photo: N/AFunding agency Knut and Alice Wallenberg Foundation (KAW) about Nils-Göran's research.
Photo: Kyodo/via REUTERS Nils-Göran comments the Nobel Prize in Physiology or Medicine 2016 in Swedish radio.
Mitochondria produce adenosine triphosphate (ATP), the energy currency of the cell, through the oxidative phosphorylation (OXPHOS) system. Mitochondria harbour their own genome, which encodes 13 of the OXPHOS components. The remaining components are encoded in the nucleus of the cell and imported into the mitochondria. We study the impact of mitochondrial dysfunction on disease and ageing using genetically modified mouse and fly models, molecular biology methods, and microscopy. Some examples of projects are described below.
Cancer cells show a distinct metabolism compared to normal cells, since they are optimized for enhanced growth rather than performing specific functions in the body. Cancer cells are often more sensitive than healthy cells to mitochondrial dysfunction, and inhibition of mitochondrial function can therefore be a powerful method to treat cancer. We work on the development of drugs for cancer treatment by inhibiting mitochondrial transcription and translation.
Mammalian mitochondrial DNA (mtDNA) is organized into nucleoids. We have studied the ultrastructure of these nucleoids and found that they have an irregular ellipsoidal shape and typically contain a single copy of mtDNA. We have also suggested a mechanism for how mtDNA is packaged into nucleoids. The organisation of mtDNA into nucleoids is reviewed in Kukat and Larsson, Trends Cell Biol 2013.
To regulate the expression of the 13 proteins encoded by the mtDNA, several hundred proteins need to be imported into the mitochondria. We study the molecular machinery for replication, transcription and translation of mtDNA. Post-transcriptional mechanisms seem to play an important role. For a recent review on these topics see Hällberg and Larsson, Cell Metabolism 2014.
We have created a knockin mouse with reduced proofreading activity during DNA replication. These mutator mice show increased levels of random point mutations and accumulate severe ageing phenotypes, showing that mtDNA mutations can cause a premature ageing phenotype. Different aspects of the role of mitochondria in mammalian ageing are discussed in Kauppila et al, Cell Metabolism 2017.
It has been suggested that mitochondrial dysfunction may be involved in the progressive neurodegenerative disorder Parkinson’s disease. To study this, we created several mouse models with neuron-specific inactivation of mtDNA genome maintenance, mitochondrial fusion or complex I deficiency. One of these models, the MitoPark mouse, recapitulates several features of Parkinson’s disease in humans and allows studies of disease progression.
Our research group is part of the Division of Molecular Metabolism at the Department of Medical Biochemistry and Biophysics. We are located in Biomedicum, a newly built and modern facility for experimental research. We share equipment and have joint scientific meetings with Anna Wredenberg’s group and Joanna Rorbach’s group, who are also in our division.
Our research is highly integrated with clinical activities at the Center for Inherited Metabolic Diseases (CMMS) at Karolinska University Hospital. Several members of our division have shared employments between KI and CMMS and we have regular joint workshops. Close collaborators also include Claes Gustafsson’s group and Maria Falkenberg’s group at Gothenburg University, with whom we have yearly scientific gatherings known as MitoRetreats. In addition, we have a range of additional collaborators both nationally and internationally.
Our group is frequently involved in the organisation of international conferences and events related to mitochondrial biology and diseases.
Postdoc candidates interested in our research are welcome to contact Nils-Göran directly.
For delivery of parcels, please use:
Karolinska Institutet
Department of Medical Biochemistry and Biophysics
Division of Molecular Metabolism
Biomedicum, floor 9D
Tomtebodavägen 16
171 65 Stockholm
Sweden
For written correspondence, please use:
First name and surname
Nils-Göran Larsson Group, 9D
Department of Medical Biochemistry and Biophysics
Karolinska Institutet
171 77 Stockholm
Sweden
Division of Molecular Metabolism
Biomedicum, floor 9D
Solnavägen 9
171 65 Stockholm
MitoRetreat 2023 took place on May 6-8 at Sånga- Säby, Sweden. The event gathered people from all research groups at the Division of Molecular Metabolism, Claes Gustafsson’s and Maria Falkenberg’s groups at Gothenburg University and a few other speakers including from CMMS, CNRS, Newcastle University, and MPI for Biology of Ageing.
15-19 May, EMBO Workshop "Molecular biology of mitochondrial gene maintenance and expression"
4 May, Joint workshop between CMMS, Clinical Genomics and Molecular Metabolism unit on Basic mechanisms and Disease models in metabolism
Joint workshop between CMMS, Clinical Genomics and Molecular Metabolism unit on Basic mechanisms and Disease models in metabolism.
This exciting meeting gathered world renown national and international researchers from the mitochondria field to discuss different areas of mitochondrial biology, from basic biochemistry to human disease. The conference was organized by Nils-Göran Larsson and Anna Wedell.
Joint workshop with CMMS (Center for Inherited Metabolic Disorders) and Clinical Genomics to discuss recent and ongoing projects. We also got an update on the progress of the national precision medicine initiative Genomics Medicine Sweden.
The second edition of the EMBO workshop on Molecular biology of molecular gene expression took place at Sånga-Säby, May 20-24 2018. Nils-Göran organised the event together with Antoni Barrientos, Maria Falkenberg, Michal Minzuk and Martin Ott. Many MolMet members attended the workshop.
Joint workshop between the research groups at the Division of Molecular Metabolism, the Centre for Inherited Metabolic Diseases (CMMS) at Karolinska University Hospital and Clinical Genomics at the Science for Life Laboratory (SciLifeLab).
MitoRetreat 2017 took place September 13-16 at Schloss Ringberg, Germany. The event gathered people from all research groups at the Division of Molecular Metabolism, Nils-Göran and Jim Stewart’s groups at the Max Planck Institute for Biology of Ageing, and Claes Gustafsson’s and Maria Falkenberg’s groups at Gothenburg University.
My interest in mitochondrial biology started in 1987 when I began my PhD studies of pathogenic mtDNA mutations causing mitochondrial disease in humans. In the early 1990s, it became evident to me that most key scientific issues in the mitochondrial field were poorly understood and that further progress would require basic scientific experimental approaches. I therefore decided to get proper training in biochemistry and mouse genetics and went to Stanford University as a HHMI Physician Postdoctoral Fellow in 1994.
When I returned to Sweden in 1997, I started my own research group at Karolinska Institutet and developed a series of powerful mouse models to study the in vivo role of mtDNA expression in normal physiology and disease pathophysiology. I also became interested in the role of mitochondrial dysfunction in ageing and in 2004 my group reported ground-breaking experimental evidence that increased mtDNA mutation levels have the capacity to induce premature ageing in the mouse.
In 2008, I was recruited as one of the founding Directors to the new Max Planck Institute for Biology of Ageing in Cologne, Germany, which provided an excellent infrastructure for my continued studies on the role of mitochondrial dysfunction in ageing. Between 2008 and 2015, I remained affiliated to KI and kept a small research group here. In 2016, I was recruited back to have KI as my main working place and became the head of the Department of Medical Biochemistry and Biophysics. Since 2019, I have been an external member of the Max Planck Society.
Postdoc candidates interested in our research are welcome to contact Nils-Göran directly.
In total, 16 of my former associates (9 women and 7 men) have independent scientist positions ranging from assistant to full professor:
| Name | Current position |
|---|---|
| Caroline Graff | Professor, Genetic Dementia Research, Karolinska Institutet, Sweden |
| Chan Bae Park | Associate Professor, Medical Sciences, Ajou University, Seoul, Korea |
| Maria Falkenberg | Professor, Medical Chemistry and Cell Biology, Göteborg University, Sweden |
| Jose P. Silva | Assistant Professor, Psychiatry and Behavioral Sciences, University of Miami, USA |
| Aleksandra Trifunovic | Professor (Full professor, German W3 level), Genetics, Cologne University, Germany |
| Anna Wredenberg | Assistant Professor and Clinical Consultant, Metabolic Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden |
| Fredrik Sterky | Assistant Professor, Laboratory Medicine, Göteborg University, Sweden |
| James B. Stewart | Associate Professor (Independent research group leader, German W2 level), Mitochondrial Genetics, Max Planck Institute for Biology of Ageing, Cologne, Germany |
| Marie Lagouge | Researcher Level 2 at the CNRS (National Center for Scientific Research), Paris, France |
| Arnaud Mourier | Researcher Level 1 at the CNRS (National Center for Scientific Research), Bordeaux, France |
| Metodi Metodiev | Researcher Level 1 at the INSERM (French Institute of Health and Medical Research), Paris, France |
| Benedetta Ruzzenente | Associate Professor, Université Paris Descartes - Paris 5, Paris, France |
| Inge Kühl | Researcher Level 2 at the CNRS (National Center for Scientific Research), Paris, France |
| Min Jiang | Assist Professor, West Lake Institute, China |
| Nina Bonekamp | Research Group Leader, Heidelberg University, Mannheim, Germany |
| Elisa Motori | Junior Group Leader, CECAD, Cologne Univ, Cologne, Germany |
