肌红蛋白(Mb)的主要生理功能的规范观点是,它是一种支持线粒体氧化磷酸化的氧(O2)储存蛋白,特别是当组织O2分压(pO2)下降并且Mb卸载O2时。除了O2储存/运输,最近的发现支持Mb在脂质运输和隔离中的功能,与细胞糖酵解代谢产物如乳酸(LAC)和丙酮酸(PYR)相互作用,以及在某些类型的癌细胞和棕色脂肪组织(BAT)中的“异位”表达。来自Mb敲除(Mb-/-)小鼠和生化模型的数据表明Mb的其他代谢作用,尤其是一氧化氮(NO)库的调节,BAT生物能学的调制,产热,和脂质储存表型。根据几十年来文献中的这些和其他发现,Mb的功能不限于输送O2以支持氧化磷酸化,但也用作调节细胞内pO2-和NO响应分子信号通路的O2传感器。这种范式反映了在Mb表达细胞如骨骼肌中如何观察氧化代谢和细胞调节的根本变化。心,棕色脂肪细胞,选择癌细胞。在这里,我们回顾了与Mb的生理作用相关的历史和新兴观点,并给出了工作模型,说明了Mb之间相互作用的可能重要性,气体,和小分子代谢物在调节细胞信号和生物能量学。
A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O2 partial pressure (pO2) drops and Mb offloads O2. Besides O2 storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR) , and \"ectopic\" expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb-/-) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb\'s function is not confined to delivering O2 in support of oxidative phosphorylation, but also to serve as an O2-sensor that modulates intracellular pO2- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Herein, we review historic and emerging views related to the physiological roles for Mb, and present working models illustrating the possible importance of interactions between Mb, gases, and small molecule metabolites in regulation of cell signaling and bioenergetics.