Role of SERCA and sarcolipin in adaptive muscle remodeling
Role of SERCA and sarcolipin in adaptive muscle remodeling
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DOI：
10.1152/ajpcell.00198.2021
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发表时间：
2022-03-01
影响因子：
5.5
通讯作者：
Tupling, A. Russell
中科院分区：
文献类型：
--
作者：
Chambers, Paige J.;Juracic, Emma S.;Tupling, A. Russell
肌磷脂（Sarcolipin，SLN）是一种抑制肌浆网Ca ~（2+）-ATP酶（SERCA）泵的小分子调节蛋白。当与SERCA结合时，SLN降低了SERCA的表观Ca 2+亲和力，并将SERCA Ca 2+转运与其ATP消耗解偶联。因此，SLN在改变骨骼肌松弛和能量消耗中起直接作用。有趣的是，SLN的表达在肌肉适应期间是动态的，因为SLN含量的大量增加被发现响应于发育、萎缩、超负荷和疾病。几个研究小组已经提出，SLN的增加，特别是在营养不良的肌肉中，是有害的，因为它可能会降低肌肉功能并加剧已经令人厌恶的细胞内Ca 2+水平。然而，也有重要的证据表明，增加SLN含量是一种有益的适应性机制，可在细胞应激期间保护SERCA泵并激活Ca 2+信号传导和适应性重塑。在这篇综述中，我们首先讨论了SLN在健康肌肉发育和过载过程中的作用，SLN已被证明可以激活Ca 2+信号，促进线粒体生物合成，纤维型转变和肌肉肥大。然后，关于肌肉疾病，我们总结了文献中关于SLN上调在本质上是适应性还是适应不良的差异。这篇综述首次提出了SLN兴奋效应在肌肉疾病中的概念，其中过多和过少的SLN都对肌肉健康有害。最后，激活SLN上调的潜在机制进行了讨论，特别是承认潜在的正反馈回路之间的SLN和Ca 2+信号分子。
Sarcolipin (SLN) is a small regulatory protein that inhibits the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump. When bound to SERCA, SLN reduces the apparent Ca2+ affinity of SERCA and uncouples SERCA Ca2+ transport from its ATP consumption. As such, SLN plays a direct role in altering skeletal muscle relaxation and energy expenditure. Interestingly, the expression of SLN is dynamic during times of muscle adaptation, in that large increases in SLN content are found in response to development, atrophy, overload, and disease. Several groups have suggested that increases in SLN, especially in dystrophic muscle, are deleterious as it may reduce muscle function and exacerbate already abhorrent intracellular Ca2+ levels. However, there is also significant evidence to show that increased SLN content is a beneficial adaptive mechanism that protects the SERCA pump and activates Ca2+ signaling and adaptive remodeling during times of cell stress. In this review, we first discuss the role for SLN in healthy muscle during both development and overload, where SLN has been shown to activate Ca2+ signaling to promote mitochondrial biogenesis, fiber-type shifts, and muscle hypertrophy. Then, with respect to muscle disease, we summarize the discrepancies in the literature as to whether SLN upregulation is adaptive or maladaptive in nature. This review is the first to offer the concept of SLN hormesis in muscle disease, wherein both too much and too little SLN are detrimental to muscle health. Finally, the underlying mechanisms which activate SLN upregulation are discussed, specifically acknowledging a potential positive feedback loop between SLN and Ca2+ signaling molecules.