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SUMMARY:Viscosity and macromolecular crowding affects size-dependent prote
 in diffusion and conformation in the mitochondrial matrix - Dr Werner Koop
 man | Radbound Centre for Mitochondrial Medicine 
DTSTART:20191127T150000Z
DTEND:20191127T160000Z
UID:TALK120409@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:The mitochondrial matrix constitutes a biochemical reaction en
 vironment with a highly complex structure. During normal and pathological 
 conditions\, this mitochondrial compartment displays dynamic changes in it
 s (ultra)structure and physicochemical properties\, which affect diffusion
 -limited reactions and molecular target finding. However\, there is little
  quantitative information on how the viscosity of the mitochondrial matrix
  solvent (ηsolvent) impacts on solute diffusion in living cells. This pre
 cludes a proper understanding of how mitochondrial structural and function
 al dynamics affect mitochondrial\, and thereby cellular\, functioning. It 
 was previously demonstrated that matrix-protruding folds (cristae) in the 
 mitochondrial inner membrane substantially hinder the free diffusion of fl
 uorescent proteins (FPs). Using HeLa cell lines expressing matrix-targeted
  FP-concatemers of increasing MW (AcGFP1\, AcGFP12\, AcGFP13\, AcGFP14) we
  here provide evidence that: (i) ηsolvent equals 2.69-3.32 cP\, (ii) all 
 FPs assume a molecular conformation of maximal size (“extended”)\, (ii
 i) the mitochondrial matrix fluid modulates FP diffusion in a MW-dependent
  manner via viscosity-dependent and -independent mechanisms. Treatment wit
 h chloramphenicol (CAP)\, a mitochondrial protein synthesis inhibitor that
  induces the mitochondrial unfolded protein response (UPRmito)\, 2-fold re
 duced the number of cristae and 24-fold increased ηsolvent (64.7-80.0 cP)
 . Under these conditions AcGFP14 assumed its minimal size (“compact”)\
 , compatible with macromolecular crowding. These findings support a mechan
 ism in which (combined) changes in mitochondrial nanostructure and matrix 
 viscosity modulate mitochondrial bioreactions by altering the diffusion an
 d molecular conformation of matrix solutes in a MW-dependent manner.
LOCATION:Sackler Lecture Theatre (Level 7) The Keith Peters Building\, Cam
 bridge Biomedical Campus
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