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Oxygen flux from capillary to mitochondria: integration of contemporary discoveries

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Abstract

Resting humans transport ~ 100 quintillion (1018) oxygen (O2) molecules every second to tissues for consumption. The final, short distance (< 50 µm) from capillary to the most distant mitochondria, in skeletal muscle where exercising O2 demands may increase 100-fold, challenges our understanding of O2 transport. To power cellular energetics O2 reaches its muscle mitochondrial target by dissociating from hemoglobin, crossing the red cell membrane, plasma, endothelial surface layer, endothelial cell, interstitial space, myocyte sarcolemma and a variable expanse of cytoplasm before traversing the mitochondrial outer/inner membranes and reacting with reduced cytochrome c and protons. This past century our understanding of O2’s passage across the body’s final O2 frontier has been completely revised. This review considers the latest structural and functional data, challenging the following entrenched notions: (1) That O2 moves freely across blood cell membranes. (2) The Krogh–Erlang model whereby O2 pressure decreases systematically from capillary to mitochondria. (3) Whether intramyocyte diffusion distances matter. (4) That mitochondria are separate organelles rather than coordinated and highly plastic syncytia. (5) The roles of free versus myoglobin-facilitated O2 diffusion. (6) That myocytes develop anoxic loci. These questions, and the intriguing notions that (1) cellular membranes, including interconnected mitochondrial membranes, act as low resistance conduits for O2, lipids and H+-electrochemical transport and (2) that myoglobin oxy/deoxygenation state controls mitochondrial oxidative function via nitric oxide, challenge established tenets of muscle metabolic control. These elements redefine muscle O2 transport models essential for the development of effective therapeutic countermeasures to pathological decrements in O2 supply and physical performance.

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Funding

Funding was provide by National Heart, Lung, and Blood Institute (Grant nos. HL-2-108328 and HL-137156-01).

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  1. Department of Kinesiology, College of Health and Human Sciences, Kansas State University, Manhattan, KS, 66506, USA

    David C. Poole, Timothy I. Musch & Trenton D. Colburn

  2. Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA

    David C. Poole, Timothy I. Musch & Trenton D. Colburn

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Poole, D.C., Musch, T.I. & Colburn, T.D. Oxygen flux from capillary to mitochondria: integration of contemporary discoveries. Eur J Appl Physiol 122, 7–28 (2022). https://doi.org/10.1007/s00421-021-04854-7

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