Krylova 2017 MiPschool Obergurgl

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High-resolution respirometry in diagnostic of mitochondrial complex I deficiency.

Link: MitoEAGLE

Krylova TD, Tsygankova PG, Itkis YS, Sheremet NL, Nevinitsyna TA, Mikhaylova SV, Zakharova EY (2017)

Event: MiPschool Obergurgl 2017


Complex I (CI) deficiency is one of the most common defects in OXPHOS system and representing more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for complex I deficiency are LHON and Leigh syndrome.

In this study we analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (N=3), m.3460 A>G (N=2), m.3635 G>A (N=1), m.3308 T>G (N=2), m.3472 T>C (N=1) and 2 patients with unpublished substitutions m.3945 C>A and m.14441T>C. High-resolution respirometry (HRR) on the Oxygraph-2k (Oroboros Instruments, Austria) was performed for complex analysis of mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls.

Flux control rations in intact cells R/E, (R-L)/E (p<0,05) were raised compared to the control. Rates R, E, L normalized on the citrate synthase activity (CS) were statistically varied between patients and controls. In permeabilized fibroblasts we observed differences in Π‘II/E, Rot/E, R/CII, CI/CII (p<0,05) between groups. These data highlight the dysfunction of OXPHOS system and particularly CI. Increased CS level and decreased CI/CII ratio indicate compensatory metabolic answer on respiratory chain dysfunction.

Our results show the facilities of HRR in revealing the biochemical abnormalities of complex I in patient’s fibroblasts with LHON and Leigh-like syndrome. We also suggest HRR to be useful method for inspection other mutations causing complex I deficiency.

β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: RU Moscow Itkis YS

Labels: MiParea: Respiration, mtDNA;mt-genetics, mt-Medicine 

Tissue;cell: Endothelial;epithelial;mesothelial cell, Fibroblast  Preparation: Intact cells, Permeabilized cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: N, S  HRR: Oxygraph-2k  Event: B2, Poster 


(1)Krylova TD, (1)Tsygankova PG, (1)Itkis YS, (2)Sheremet NL, (2)Nevinitsyna TA, (3)Mikhaylova SV, (1)Zakharova EY1
  1. Res Centre Med Gen
  2. Res Inst Eye Dis
  3. Rus Child Clin Hosp
Moscow, Russia. – [email protected]
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