Mitochondrial membrane potential is regulated by vimentin intermediate filaments.

Area of Science:

• Cell Biology
• Mitochondrial Biology
• Cytoskeletal Dynamics

Background:

• Mitochondria are key organelles for cellular energy production.
• Vimentin intermediate filaments (VIFs) are crucial components of the cellular cytoskeleton.
• The physical association between mitochondria and VIFs is known but its functional significance is not fully understood.

Purpose of the Study:

• To investigate the functional impact of the association between mitochondria and vimentin intermediate filaments.
• To quantify the effect of vimentin on mitochondrial membrane potential.
• To identify the specific vimentin domains responsible for mitochondrial interaction.

Main Methods:

• Quantitative fluorescence microscopy using tetramethylrhodamine-ethyl ester (TMRE) to measure mitochondrial membrane potential.
• Comparison of TMRE fluorescence in vimentin-null fibroblasts versus cells expressing vimentin.
• Assessment of mitochondrial membrane potential in cells with silenced vimentin expression using small hairpin RNA (shRNA).
• Analysis of mitochondrial membrane potential in rho 0 cells (lacking mtDNA) to assess the role of the respiratory chain.

Main Results:

• Association with VIFs increased mitochondrial membrane potential by approximately 35%.
• Reduced vimentin expression (by 90%) led to a 20% decrease in mitochondrial membrane potential.
• A specific subdomain (residues 40-93) of the vimentin N terminus mediates the interaction with mitochondria.
• In rho 0 cells, mitochondrial membrane potential was insensitive to VIF interactions, indicating dependence on the respiratory chain.

Conclusions:

• The physical association between mitochondria and VIFs is critical for regulating mitochondrial membrane potential.
• Vimentin's N-terminal region is essential for its interaction with mitochondria.
• This interaction influences both the localization and physiological activity of mitochondria within the cell.