Department of Kinesiology, College of Health and Human Sciences, Kansas State University, Manhattan, KS, 66506, USA.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
Eur J Appl Physiol. 2022 Jan;122(1):7-28. doi: 10.1007/s00421-021-04854-7. Epub 2021 Dec 23.
Resting humans transport ~ 100 quintillion (10) oxygen (O) 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 O demands may increase 100-fold, challenges our understanding of O transport. To power cellular energetics O 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 O's passage across the body's final O frontier has been completely revised. This review considers the latest structural and functional data, challenging the following entrenched notions: (1) That O moves freely across blood cell membranes. (2) The Krogh-Erlang model whereby O 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 O 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 O, 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 O transport models essential for the development of effective therapeutic countermeasures to pathological decrements in O supply and physical performance.
静息状态下的人体每秒钟向组织输送约 10 的 20 次方（10 后面 20 个 0）个氧（O）分子以供消耗。在骨骼肌中，从毛细血管到最远端的线粒体的最后短距离（<50μm），运动时的 O 需求可能会增加 100 倍，这对我们对 O 传输的理解构成了挑战。为了为细胞能量供应提供动力，O 通过与血红蛋白分离、穿过红细胞膜、血浆、内皮表面层、内皮细胞、细胞间隙、肌细胞膜和细胞质的可变区域，然后穿过线粒体的内外膜并与还原型细胞色素 c 和质子反应，从而到达肌肉线粒体的靶标。在过去的一个世纪中，我们对 O 穿过身体最后 O 前沿的理解已经完全被修正。这篇综述考虑了最新的结构和功能数据，挑战了以下根深蒂固的观念：（1）O 可以自由穿过细胞膜。（2）O 压力从毛细血管到线粒体系统地降低的 Krogh-Erlang 模型。（3）肌细胞内扩散距离是否重要。（4）线粒体是独立的细胞器，而不是协调和高度可塑的合胞体。（5）自由 O 扩散与肌红蛋白促进的 O 扩散的作用。（6）肌细胞会出现缺氧区域。这些问题以及有趣的观念，即（1）细胞膜，包括相互连接的线粒体膜，作为 O、脂质和 H-电化学运输的低电阻通道，以及（2）肌红蛋白的氧合/去氧合状态通过一氧化氮控制线粒体的氧化功能，挑战了肌肉代谢控制的既定原则。这些因素重新定义了肌肉 O 传输模型，对于开发有效治疗病理性 O 供应和身体表现下降的治疗方法至关重要。
