Stress‐dependent macromolecular crowding in the mitochondrial matrix

Abstract: Macromolecules of various sizes induce crowding of the cellular environment. This crowding impacts on biochemical reactions by increasing solvent viscosity, decreasing the water‐accessible volume and altering protein shape, function, and interactions. Although mitochondria represent highly protein‐rich organelles, most of these proteins are somehow immobilized. Therefore, whether the mitochondrial matrix solvent exhibits macromolecular crowding is still unclear. Here, we demonstrate that fluorescent protein fusion peptides (AcGFP1 concatemers) in the mitochondrial matrix of HeLa cells display an elongated molecular structure and that their diffusion constant decreases with increasing molecular weight in a manner typical of macromolecular crowding. Chloramphenicol (CAP) treatment impaired mitochondrial function and reduced the number of cristae without triggering mitochondrial orthodox‐to‐condensed transition or a mitochondrial unfolded protein response. CAP‐treated cells displayed progressive concatemer immobilization with increasing molecular weight and an eightfold matrix viscosity increase, compatible with increased macromolecular crowding. These results establish that the matrix solvent exhibits macromolecular crowding in functional and dysfunctional mitochondria. Therefore, changes in matrix crowding likely affect matrix biochemical reactions in a manner depending on the molecular weight of the involved crowders and reactants.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Stress‐dependent macromolecular crowding in the mitochondrial matrix ; day:24 ; month:02 ; year:2023 ; extent:24
The EMBO journal / European Molecular Biology Organization ; (24.02.2023) (gesamt 24)

Creator
Bulthuis, Elianne P.
Dieteren, Cindy E. J.
Bergmans, Jesper
Berkhout, Job
Wagenaars, Jori A.
van de Westerlo, Els M. A.
Podhumljak, Emina
Hink, Mark A.
Hesp, Laura F. B.
Rosa, Hannah S.
Malik, Afshan N.
Lindert, Mariska Kea‐te
Willems, Peter H. G. M.
Gardeniers, Han
den Otter, Wouter K.
Adjobo‐Hermans, Merel J. W.
Koopman, Werner J. H.

DOI
10.15252/embj.2021108533
URN
urn:nbn:de:101:1-2023022414285931228835
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:56 AM CEST

Data provider

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Associated

  • Bulthuis, Elianne P.
  • Dieteren, Cindy E. J.
  • Bergmans, Jesper
  • Berkhout, Job
  • Wagenaars, Jori A.
  • van de Westerlo, Els M. A.
  • Podhumljak, Emina
  • Hink, Mark A.
  • Hesp, Laura F. B.
  • Rosa, Hannah S.
  • Malik, Afshan N.
  • Lindert, Mariska Kea‐te
  • Willems, Peter H. G. M.
  • Gardeniers, Han
  • den Otter, Wouter K.
  • Adjobo‐Hermans, Merel J. W.
  • Koopman, Werner J. H.

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