Partial complex I inhibition decreases mitochondrial motility and increases matrix protein diffusion as revealed by fluorescence correlation spectroscopy

W.J.H. Koopman, M.A. Hink, S. Verkaart, H.J. Visch, J.A.M. Smeitink, Phgm Willems

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21 Citations (Scopus)

Abstract

We previously reported that inhibition of mitochondrial complex I (CI) by rotenone induces marked increases in mitochondrial length and degree of branching, thus revealing a relationship between mitochondrial function and shape. We here describe the first time use of fluorescence correlation spectroscopy (FCS) to simultaneously probe mitochondrial mobility and intra-matrix protein diffusion, with the aim to investigate the effects of chronic CI inhibition on the latter two parameters. To this end, EYTP was expressed in the mitochondrial matrix of human skin fibroblasts (mitoEYFP) using baculoviral transduction and its diffusion monitored by FCS. This approach revealed the coexistence of moving and stationary mitochondria within the same cell and enabled simultaneous quantification of mitochondrial velocity and mitoEYFP diffusion. When Cl activity was chronically reduced by 80% using rotenone treatment, the percentage of moving mitochondria and their velocity decreased by 30%. MitoEYFP diffusion did not differ between moving and stationary mitochondria but was increased 2-fold in both groups of mitochondria following rotenone treatment. We propose that the increase in matrix protein diffusion together with the increase in mitochondrial length and degree of branching constitutes part of an adaptive response which serves to compensate for the reduction in CI activity and mitochondrial motility.
Original languageEnglish
Pages (from-to)940-947
JournalBiochimica et Biophysica Acta. B, Bioenergetics
Volume1767
Issue number7
DOIs
Publication statusPublished - 2007

Keywords

  • correlation microscopy
  • transmitting cables
  • liver mitochondria
  • mammalian-cells
  • atp production
  • living cells
  • dynamics
  • deficiency
  • microtubule
  • transport

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