External Member: Larsson Adjunct Group

Mitochondrial Biology

Mitochondria are cell organelles that are central to metabolism and have their own genetic material, mitochondrial DNA. In our research group, we investigate the molecular mechanisms responsible for the maintenance of mitochondrial DNA and analyse the impact of mitochondrial dysfunction on disease and ageing.

Mitochondrial dysfunction is heavily implicated in the ageing process. Ageing humans have increased levels of somatic mtDNA mutations that typically undergo clonal expansion to cause mosaic patterns of respiratory chain deficiency in affected organs. The oxidative phosphorylation (OXPHOS) system produces adenosine triphosphate (ATP), the universal energy currency in mammalian tissues. The OXPHOS system is composed of two functional entities, i.e. the respiratory chain (complexes I-IV) and the phosphorylation system, which includes the ATP synthase (complex V). Transporting electrons through complex I-IV is coupled to the creation of a proton gradient, which drives the ATP synthesis by complex V. Respiratory chain dysfunction, and thus insufficient supply of ATP, can cause a variety of phenotypes associated with ageing and age-related mitochondrial diseases.

Mitochondria harbor their own genome, which is ~16 kb in mammals. Animal mitochondrial DNA (mtDNA) typically encodes 2 ribosomal RNAs (rRNAs) and 22 transfer RNAs (tRNAs). Furthermore, it encodes 13 proteins, which are all components of the oxidative phosphorylation system. The remaining proteins of the OXPHOS system are nuclear encoded. Respiratory chain proteins form complexes that are located in the inner membrane of mitochondria in a dynamic system in which the individual complexes coexist with superassembled structures.

In the group of Nils-Göran Larsson, we use the house mouse (Mus musculus) as a model organism to investigate mechanisms controlling mtDNA maintenance and the functional role of superassemblies of respiratory chain complexes.

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