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Signaling of mitochondrial DNA instability

Research group Our group is interested in the causes and consequences of mtDNA instability.

The genetic information encoded in our second genome, the mitochondrial DNA (mtDNA), is required for efficient energy production. Defects in mtDNA can alter cellular energy metabolism, and are associated with several genetic diseases as well as some forms of cancer. Our group is interested in the causes and consequences of mtDNA instability, especially how mtDNA instability is signaled to the rest of the cell.

We use a combination of in vitro biochemistry, mammalian cell culture and yeast genetics to explore the basic mechanisms that ensure the maintenance of this small but essential genome.

Mitochondria – the energy factories of our cells – contain their own distinct genome that is essential for efficient energy production. MtDNA defects such as mutations, deletions or depletion cause a wide variety of rare genetic disorders, and have also been associated with more common disease states like neurodegenerative diseases and some cancers.

The mtDNA is constantly exposed to various endogenous and exogenous insults that jeopardize its stability and may lead to alteration or loss of the genetic information encoded in this vitally important molecule. Known causes of mtDNA instability include reactive oxygen species, radiation and toxic chemicals, but also replication errors that can arise from e.g. defects in the machinery that catalyzes mtDNA replication or a shortage or imbalance of the DNA building blocks, dNTPs.

The major aim of our work is to increase our understanding of the variety of mechanisms that either prevent, or help cope with, various forms of mtDNA instability.

Our research projects address an array of questions related to mtDNA instability, ranging from the requirements for faithful mtDNA replication and the effects of incorporated ribonucleotides to the cellular consequences of mtDNA instability. A major focus of our work is to address the types of signals and the cellular consequences that are triggered upon mtDNA instability. We use two complementary biological systems in our studies: baker’s yeast Saccharomyces cerevisiae as well as cultured human cells in order to facilitate the identification of signals and factors involved in mito-cellular communication.

Furthermore, we make use of our expertise in biochemistry to study the mechanistic details of this communication using purified recombinant proteins in relevant in vitro assays.

To find out more about our research group, please visit our website.

Head of research

Paulina Wanrooij
Research fellow
E-mail
Email

Overview

Participating departments and units at Umeå University

Department of Medical Biochemistry and Biophysics

Research area

Cancer, Molecular biology and genetics
Research on cells' power plants and cancer receives funding

Paulina Wanrooij named new Wallenberg Academy Fellow and Nasim Sabouri gets another five-years of funding.