Probing the outer mitochondrial membrane in cardiac mitochondria with nanoparticles

Area of Science:

• Mitochondrial Biology
• Cellular Physiology
• Apoptosis Regulation

Background:

• The outer mitochondrial membrane (OMM) is crucial for cellular integrity and apoptosis.
• OMM breaches release cytochrome c oxidase, initiating programmed cell death.
• Understanding OMM permeability is key to cellular regulation.

Purpose of the Study:

• To precisely determine the pore size of the voltage-dependent anion channel (VDAC) in the OMM.
• To investigate OMM permeability under physiological conditions and during permeability transition.
• To elucidate factors affecting VDAC pore availability within cardiac cells.

Main Methods:

• Utilized calibrated gold nanoparticles (3-nm and 6-nm) to probe OMM permeability.
• Employed rat permeabilized ventricular cells and isolated cardiac mitochondria.
• Investigated the role of VDAC inhibitors (König polyanion, DIDS) and intracellular barriers.

Main Results:

• The OMM is impermeable to 6-nm particles but permeable to 3-nm particles.
• 3-nm particle entry into the intermembrane space is mediated by VDAC.
• VDAC pore size is estimated to be between 3-nm and 6-nm.
• Intracellular barriers significantly restrict VDAC pore availability in intact cells.
• Permeability transition leads to OMM disruption and swelling.

Conclusions:

• VDAC pore diameter in cardiac mitochondria is between 3-nm and 6-nm.
• Intracellular factors limit VDAC accessibility, impacting mitochondrial permeability.
• Mitochondrial swelling during permeability transition compromises OMM integrity.