Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria

W.J.H. Koopman, F. Distelmaier, M.A. Hink, S. Verkaart, M. Wijers, J. Fransen, J.A.M. Smeitink, P.H.G.M. Willems

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)


Mitochondria continuously change shape, position, and matrix configuration for optimal metabolite exchange. It is well established that changes in mitochondrial metabolism influence mitochondrial shape and matrix configuration. We demonstrated previously that inhibition of mitochondrial complex I (CI or NADH: ubiquinone oxidoreductase) by rotenone accelerated matrix protein diffusion and decreased the fraction and velocity of moving mitochondria. In the present study, we investigated the relationship between inherited CI deficiency, mitochondrial shape, mobility, and matrix protein diffusion. To this end, we analyzed fibroblasts of two children that represented opposite extremes in a cohort of 16 patients, with respect to their residual CI activity and mitochondrial shape. Fluorescence correlation spectroscopy (FCS) revealed no relationship between residual CI activity, mitochondrial shape, the fraction of moving mitochondria, their velocity, and the rate of matrix-targeted enhanced yellow fluorescent protein (mitoEYFP) diffusion. However, mitochondrial velocity and matrix protein diffusion in moving mitochondria were two to three times higher in patient cells than in control cells. Nocodazole inhibited mitochondrial movement without altering matrix EYFP diffusion, suggesting that both activities are mutually independent. Unexpectedly, electron microscopy analysis revealed no differences in mitochondrial ultrastructure between control and patient cells. It is discussed that the matrix of a moving mitochondrion in the CI-deficient state becomes less dense, allowing faster metabolite diffusion, and that fibroblasts of CI-deficient patients become more glycolytic, allowing a higher mitochondrial velocity.
Original languageEnglish
Pages (from-to)C1124-C1132
JournalAmerican Journal of Physiology: Cell Physiology
Issue number5
Publication statusPublished - 2008


  • fluorescence correlation spectroscopy
  • ubiquinone oxidoreductase deficiency
  • leigh-syndrome
  • human nadh
  • oxidative-phosphorylation
  • correlation microscopy
  • skin fibroblasts
  • steady-state
  • mutations
  • motility


Dive into the research topics of 'Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria'. Together they form a unique fingerprint.

Cite this