Bal Naresh C, Gupta Subash C, Pant Meghna, Sopariwala Danesh H, Gonzalez-Escobedo Geoffrey, Turner Joanne, Gunn John S, Pierson Christopher R, Harper Scott Q, Rafael-Fortney Jill A, Periasamy Muthu
School of Biotechnology, KIIT University, Bhubaneswar, India.
Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, United States.
Front Physiol. 2021 Mar 1;12:633058. doi: 10.3389/fphys.2021.633058. eCollection 2021.
Sarcolipin (SLN) is a regulator of sarco/endo plasmic reticulum Ca-ATPase (SERCA) pump and has been shown to be involved in muscle nonshivering thermogenesis (NST) and energy metabolism. Interestingly, SLN expression is significantly upregulated both during muscle development and in several disease states. However, the significance of altered SLN expression in muscle patho-physiology is not completely understood. We have previously shown that transgenic over-expression of SLN in skeletal muscle is not detrimental, and can promote oxidative metabolism and exercise capacity. In contrast, some studies have suggested that SLN upregulation in disease states is deleterious for muscle function and ablation of SLN can be beneficial. In this perspective article, we critically examine both published and some new data to determine the relevance of SLN expression to disease pathology. The new data presented in this paper show that SLN levels are induced in muscle during systemic bacterial () infection or lipopolysaccharides (LPS) treatment. We also present data showing that SLN expression is significantly upregulated in different types of muscular dystrophies including myotubular myopathy. These data taken together reveal that upregulation of SLN expression in muscle disease is progressive and increases with severity. Therefore, we suggest that increased SLN expression should not be viewed as the cause of the disease; rather, it is a compensatory response to meet the higher energy demand of the muscle. We interpret that higher SLN/SERCA ratio positively modulate cytosolic Ca signaling pathways to promote mitochondrial biogenesis and oxidative metabolism to meet higher energy demand in muscle.
肌脂蛋白（SLN）是肌浆/内质网Ca - ATP酶（SERCA）泵的一种调节因子，已被证明参与肌肉非寒战产热（NST）和能量代谢。有趣的是，SLN的表达在肌肉发育过程中和几种疾病状态下均显著上调。然而，SLN表达改变在肌肉病理生理学中的意义尚未完全明确。我们之前已经表明，在骨骼肌中转基因过表达SLN并无损害，反而可以促进氧化代谢和运动能力。相比之下，一些研究表明，在疾病状态下SLN上调对肌肉功能有害，而敲除SLN可能有益。在这篇观点文章中，我们批判性地审视了已发表的和一些新的数据，以确定SLN表达与疾病病理的相关性。本文所呈现的新数据表明，在全身细菌感染或脂多糖（LPS）处理期间，肌肉中的SLN水平会升高。我们还展示了数据，表明在包括肌管性肌病在内的不同类型的肌肉营养不良症中，SLN表达显著上调。综合这些数据揭示，在肌肉疾病中SLN表达上调是渐进性的，且随着疾病严重程度增加。因此，我们认为SLN表达增加不应被视为疾病的原因；相反，它是一种为满足肌肉更高能量需求的代偿性反应。我们推断，较高的SLN/SERCA比值正向调节胞质Ca信号通路，以促进线粒体生物发生和氧化代谢，从而满足肌肉中更高的能量需求。
