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Mitochondrial and Cardiovascular Physiopathology | UMR Inserm U1083 - CNRS 6015

Separated by coma


Mitochondrial complex I deficiencies: From diagnosis to therapeutic screening

State of the art and objectives

Involved in the biochemical and molecular diagnosis of mitochondrial disorders in the Department of Biochemistry and Genetics and the reference center for mitochondrial diseases at the University Hospital of Angers, we develop a translational research focused on complex I (CI) deficiencies and metabolic reprogramming.

Among mitochondrial diseases, complex I (CI) deficiency is the most commonly found in up to 30% of patients, leading to drastic energetic impairment. In order to adapt their metabolism to environmental conditions, cells must possess a metabolic flexibility to rewire energetic metabolic pathways according to substrate or oxygen availability or oxidative stress. We demonstrated that this metabolic flexibility was impeded in CI patients and that the metabolic rewiring set up to cope with energetic impairment mainly relies on a correct assembly of all the respiratory chain complex subunits.

With the goal of identifying new diagnosis biomarkers and therapeutic targets, we take advantage of a large cohort of patient fibroblasts suffering from CI deficiencies to study the link between the structure and the function mitochondrial complex I and the metabolic adaptations set up to cope with energetic impairment paying a particular attention on redox (NAD+/NADH) and energetic (ATP/ADP) ratios. With the support of the Fondation Maladies Rares we are now performing a pharmacological screening that can target the identified defects in order to provide new therapeutic alternatives in disease without curative treatments nowadays.

Scientific partners : 

Mitochondrial bioinformatic 

State of the  art and objectives

  • Development of in silico tools dedicated to mitochondrial disorders diagnosis.
  • Improve mitochondrial variants prioritization by taking into account mitochondrial genome specificities.
  • Improve mitochondrial genome analysis from WES and WGS sequencing.

Scientific partners :