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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2015

Authors: Klotzsch, E; Smorodchenko, A; Löfler, L; Moldzio, R; Parkinson, E; Schütz, GJ; Pohl, EE

Title: Superresolution microscopy reveals spatial separation of UCP4 and F0F1-ATP synthase in neuronal mitochondria.

Source: Proc Natl Acad Sci U S A. 2015; 112(1):130-135



Authors Vetmeduni Vienna:

Moldzio Rudolf
Pohl Elena
Smorodchenko Alina

Vetmed Research Units
Institute for Medical Biochemistry
Institute of Physiology, Pathohysiology and Biophysics, Unit of Physiology and Biophysics


Abstract:
Because different proteins compete for the proton gradient across the inner mitochondrial membrane, an efficient mechanism is required for allocation of associated chemical potential to the distinct demands, such as ATP production, thermogenesis, regulation of reactive oxygen species (ROS), etc. Here, we used the superresolution technique dSTORM (direct stochastic optical reconstruction microscopy) to visualize several mitochondrial proteins in primary mouse neurons and test the hypothesis that uncoupling protein 4 (UCP4) and F0F1-ATP synthase are spatially separated to eliminate competition for the proton motive force. We found that UCP4, F0F1-ATP synthase, and the mitochondrial marker voltage-dependent anion channel (VDAC) have various expression levels in different mitochondria, supporting the hypothesis of mitochondrial heterogeneity. Our experimental results further revealed that UCP4 is preferentially localized in close vicinity to VDAC, presumably at the inner boundary membrane, whereas F0F1-ATP synthase is more centrally located at the cristae membrane. The data suggest that UCP4 cannot compete for protons because of its spatial separation from both the proton pumps and the ATP synthase. Thus, mitochondrial morphology precludes UCP4 from acting as an uncoupler of oxidative phosphorylation but is consistent with the view that UCP4 may dissipate the excessive proton gradient, which is usually associated with ROS production.

Keywords Pubmed: Animals
Membrane Potential, Mitochondrial
Membrane Transport Proteins/metabolism*
Mice
Microscopy/methods*
Mitochondria/metabolism*
Mitochondrial Membranes/metabolism
Mitochondrial Uncoupling Proteins
Neurons/metabolism*
Proton-Translocating ATPases/metabolism*
Protons
Voltage-Dependent Anion Channels/metabolism


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