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Mitochondrial methylation and its role in health and disease

Objective

Mitochondria and mitochondrial function have gained increased attention within a wide range of clinical and scientific specialities, but exactly how mitochondria impact the rest of the cell is less well understood. Not only are mitochondria implicated in a range of rare genetic disorders, but dysfunction of mitochondria or reduced bioenergetic capacity has been associated with common diseases including cancer, heart failure, neurodegeneration and diabetes mellitus, as well as natural ageing. It is becoming increasingly clear that mitochondrial dysfunction is not only a downstream event in these conditions, but plays an important role in disease progression and pathology.

S-adenosylmethionine (SAM) is the dominant methyl group donor within our cells, required for a diverse set of post-translational modifications, nucleotide methylations or the synthesis of co-factors and metabolites. Mitochondria play an important part in SAM synthesis, and mitochondrial function has recently been shown to influence cellular methylation. Approximately 30% of the cellular SAM pool is located within mitochondria, advocating a central role for mitochondria in cellular methylation. The advancements in genome sequencing techniques, unprecedented depth of modern mass spectrometry analyses and our possibility to efficiently generate model systems, provides a rare opportunity to comprehensively study the role of both SAM and mitochondria in health and disease.

This project plan describes the genetic, molecular, metabolic and proteomic analysis of fruit fly and mouse models with mitochondrial dysfunction and disrupted intra-mitochondrial SAM levels to identify the mitochondrial methylome, its relevance towards other cellular functions and its impact on the epigenetic control of gene regulation. My extensive research on mitochondrial function, as well as working as a physician with patients suffering from inborn errors of metabolism gives me a unique perspective in this project.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/clinical medicine/endocrinology/diabetes
  • /natural sciences/chemical sciences/organic chemistry/amines
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics
  • /natural sciences/chemical sciences/analytical chemistry/mass spectrometry
  • /agricultural sciences/agriculture, forestry, and fisheries/agriculture/horticulture/fruit growing
  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/genetics and heredity/nucleotide

Call for proposal

ERC-2016-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 499 999,25

Beneficiaries (1)

KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 1 499 999,25
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments