Laboratory of Cardiac Energetics, NHLBI, NIH, Bethesda, MD 20892-1061, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 May;302(9):R1034-48. doi: 10.1152/ajpregu.00596.2011. Epub 2012 Feb 29.
The concentration of mitochondrial oxidative phosphorylation complexes (MOPCs) is tuned to the maximum energy conversion requirements of a given tissue; however, whether the activity of MOPCs is altered in response to acute changes in energy conversion demand is unclear. We hypothesized that MOPCs activity is modulated by tissue metabolic stress to maintain the energy-metabolism homeostasis. Metabolic stress was defined as the observed energy conversion rate/maximum energy conversion rate. The maximum energy conversion rate was assumed to be proportional to the concentration of MOPCs, as determined with optical spectroscopy, gel electrophoresis, and mass spectrometry. The resting metabolic stress of the heart and liver across the range of resting metabolic rates within an allometric series (mouse, rabbit, and pig) was determined from MPOCs content and literature respiratory values. The metabolic stress of the liver was high and nearly constant across the allometric series due to the proportional increase in MOPCs content with resting metabolic rate. In contrast, the MOPCs content of the heart was essentially constant in the allometric series, resulting in an increasing metabolic stress with decreasing animal size. The MOPCs activity was determined in native gels, with an emphasis on Complex V. Extracted MOPCs enzyme activity was proportional to resting metabolic stress across tissues and species. Complex V activity was also shown to be acutely modulated by changes in metabolic stress in the heart, in vivo and in vitro. The modulation of extracted MOPCs activity suggests that persistent posttranslational modifications (PTMs) alter MOPCs activity both chronically and acutely, specifically in the heart. Protein phosphorylation of Complex V was correlated with activity inhibition under several conditions, suggesting that protein phosphorylation may contribute to activity modulation with energy metabolic stress. These data are consistent with the notion that metabolic stress modulates MOPCs activity in the heart.
线粒体氧化磷酸化复合物（MOPCs）的浓度根据特定组织的最大能量转换需求进行调整；然而，MOPCs 的活性是否会响应能量转换需求的急性变化而改变尚不清楚。我们假设 MOPCs 的活性通过组织代谢应激来调节，以维持能量代谢平衡。代谢应激定义为观察到的能量转换率/最大能量转换率。最大能量转换率被认为与 MOPCs 的浓度成正比，这是通过光学光谱、凝胶电泳和质谱来确定的。通过 MPOCs 含量和文献呼吸值，从心脏和肝脏在一个体型系列（小鼠、兔子和猪）中的静息代谢率范围内确定静息代谢应激。由于 MOPCs 含量与静息代谢率成正比，因此肝脏的代谢应激在整个体型系列中都很高且几乎保持不变。相比之下，心脏的 MOPCs 含量在体型系列中基本保持不变，导致代谢应激随动物体型的减小而增加。在天然凝胶中测定 MOPCs 活性，重点是复合物 V。提取的 MOPCs 酶活性与组织和物种的静息代谢应激成正比。体内和体外实验还表明，心脏中的代谢应激会急性调节复合物 V 的活性。提取的 MOPCs 活性的调节表明，持续的翻译后修饰（PTMs）会慢性和急性地改变 MOPCs 的活性，特别是在心脏中。在几种情况下，复合物 V 的蛋白磷酸化与活性抑制相关，表明蛋白磷酸化可能有助于能量代谢应激时的活性调节。这些数据与代谢应激调节心脏中 MOPCs 活性的观点一致。
