scholarly journals Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state

2012 ◽  
Vol 31 (14) ◽  
pp. 3169-3182 ◽  
Author(s):  
Kerstin Kojer ◽  
Melanie Bien ◽  
Heike Gangel ◽  
Bruce Morgan ◽  
Tobias P Dick ◽  
...  
Keyword(s):  
Redox Potential ◽  
Redox State ◽  
Intermembrane Space ◽  
Mitochondrial Intermembrane Space ◽  
Glutathione Redox

scholarly journals A Thioredoxin reductive mechanism balances the oxidative protein import pathway in the intermembrane space of mitochondria

2021 ◽  
Author(s):  
Mauricio Cardenas-Rodriguez ◽  
Phanee Manganas ◽  
Emmanouela Kallergi ◽  
Ruairidh Edwards ◽  
Afroditi Chatzi ◽  
...  
Keyword(s):  
Redox State ◽  
Protein Import ◽  
Interaction Analysis ◽  
Oxidative Capacity ◽  
Intermembrane Space ◽  
Thioredoxin System ◽  
In Vitro Reconstitution ◽  
Mitochondrial Intermembrane Space ◽  
Mitochondria Biogenesis

Mitochondria biogenesis crucially depends on the oxidative folding system in the mitochondrial intermembrane space. The oxidative capacity needs however to be balanced by a reductive pathway for optimal mitochondrial fitness. Here we report that the cytosolic thioredoxin machinery fulfils this critical reductive function by dual localisation in the mitochondrial intermembrane space (IMS) via an unconventional import pathway. We show that the presence of the Thioredoxin system in the IMS mediates a hitherto unknown communication between mitochondria biogenesis and the metabolic state of the cell via the cytosolic pool of NADPH. By a combination of complete in vitro reconstitution with purified components, import assays and protein interaction analysis we find that the IMS-localised thioredoxin machinery critically controls the redox state of Mia40, the key player in the MIA pathway in mitochondria thereby ensuring optimal mitochondria biogenesis. Intriguingly, we find that the IMS thioredoxin system fulfils a previously unknown role in the retrograde release of structurally destabilised proteins into the cytosol and protection against oxidative damage, both of which serve as critical mechanisms of mitochondrial surveillance and quality control.

Acute nutrient regulation of the mitochondrial glutathione redox state in pancreatic β-cells

2014 ◽  
Vol 460 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Hilton K. Takahashi ◽  
Laila R. B. Santos ◽  
Letícia P. Roma ◽  
Jessica Duprez ◽  
Christophe Broca ◽  
...  
Keyword(s):  
Redox Potential ◽  
Redox State ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Nutrient Regulation ◽  
Mitochondrial Glutathione ◽  
Glutathione Redox

Nutrient stimulation acutely reduces mitochondrial, but not cytosolic/nuclear, glutathione redox potential (EGSH) in insulin-secreting β-cells under control conditions. These changes are negatively correlated with NAD(P)H autofluorescence, but independent from changes in intracellular Ca2+ or mitochondrial pH.

scholarly journals Kinetic control by limiting glutaredoxin amounts enables thiol oxidation in the reducing mitochondrial intermembrane space

2015 ◽  
Vol 26 (2) ◽  
pp. 195-204 ◽  
Author(s):  
Kerstin Kojer ◽  
Valentina Peleh ◽  
Gaetano Calabrese ◽  
Johannes M. Herrmann ◽  
Jan Riemer
Keyword(s):  
Redox State ◽  
Protein Import ◽  
Kinetic Control ◽  
Intermembrane Space ◽  
Mitochondrial Import ◽  
Oxidative Folding ◽  
Mitochondrial Intermembrane Space ◽  
Reducing Environment ◽  
Targeting Signals ◽  
Main Component

The mitochondrial intermembrane space (IMS) harbors an oxidizing machinery that drives import and folding of small cysteine-containing proteins without targeting signals. The main component of this pathway is the oxidoreductase Mia40, which introduces disulfides into its substrates. We recently showed that the IMS glutathione pool is maintained as reducing as that of the cytosol. It thus remained unclear how equilibration of protein disulfides with the IMS glutathione pool is prevented in order to allow oxidation-driven protein import. Here we demonstrate the presence of glutaredoxins in the IMS and show that limiting amounts of these glutaredoxins provide a kinetic barrier to prevent the thermodynamically feasible reduction of Mia40 substrates by the IMS glutathione pool. Moreover, they allow Mia40 to exist in a predominantly oxidized state. Consequently, overexpression of glutaredoxin 2 in the IMS results in a more reduced Mia40 redox state and a delay in oxidative folding and mitochondrial import of different Mia40 substrates. Our findings thus indicate that carefully balanced glutaredoxin amounts in the IMS ensure efficient oxidative folding in the reducing environment of this compartment.

scholarly journals Optogenetic Monitoring of the Glutathione Redox State in Engineered Human Myocardium

2019 ◽  
Vol 10 ◽  
Author(s):  
Irina Trautsch ◽  
Eriona Heta ◽  
Poh Loong Soong ◽  
Elif Levent ◽  
Viacheslav O. Nikolaev ◽  
...  
Keyword(s):  
Redox State ◽  
Human Myocardium ◽  
Glutathione Redox

scholarly journals Proteomic Mapping of the Human Mitochondrial Intermembrane Space in Live Cells via Ratiometric APEX Tagging

2014 ◽  
Vol 55 (2) ◽  
pp. 332-341 ◽  
Author(s):  
Victoria Hung ◽  
Peng Zou ◽  
Hyun-Woo Rhee ◽  
Namrata D. Udeshi ◽  
Valentin Cracan ◽  
...  
Keyword(s):  
Live Cells ◽  
Intermembrane Space ◽  
Mitochondrial Intermembrane Space

scholarly journals The Mitochondrial Intermembrane Space Oxireductase Mia40 Funnels the Oxidative Folding Pathway of the CytochromecOxidase Assembly Protein Cox19

2014 ◽  
Vol 289 (14) ◽  
pp. 9852-9864 ◽  
Author(s):  
Hugo Fraga ◽  
Joan-Josep Bech-Serra ◽  
Francesc Canals ◽  
Gabriel Ortega ◽  
Oscar Millet ◽  
...  
Keyword(s):  
Folding Pathway ◽  
Intermembrane Space ◽  
Oxidative Folding ◽  
Mitochondrial Intermembrane Space

The Yeast Mitochondrial Intermembrane Space: Purification and Analysis of Two Distinct Fractions

1998 ◽  
Vol 265 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Heiko Martin ◽  
Christoph Eckerskorn ◽  
Frank Gärtner ◽  
Joachim Rassow ◽  
Fritz Lottspeich ◽  
...  
Keyword(s):  
Intermembrane Space ◽  
Mitochondrial Intermembrane Space
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