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Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O 2 in tissue depends on its solubility and diffusivity in complex and heterogeneous macromolecular environments. The path of oxygen diffusion is key to its rate of transfer, especially where pathways of differing favorability are present. Most commonly, aqueous media, such as interstitial fluid and cytoplasm, are assumed to provide the dominant diffusion path. Here, the 'hydrophobic channeling' hypothesis is revisited, and several lines of evidence pointing toward lipid-accelerated oxygen diffusion pathways are discussed. The implications of hydrophobic channeling are considered in light of extended membrane networks in cells and tissues.

Pathways of Oxygen Diffusion in Cells and Tissues