Buffering roles of (pro)renin receptor in starvation-induced autophagy of skeletal muscles.
Buffering roles of (pro)renin receptor in starvation-induced autophagy of skeletal muscles.
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DOI：
10.14814/phy2.13587
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发表时间：
2018-03
影响因子：
2.5
通讯作者：
Ichihara A
中科院分区：
文献类型：
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作者：
Mizuguchi Y;Yatabe M;Morishima N;Morimoto S;Ichihara A
自噬是一种细胞内的分解代谢过程，有助于调节营养平衡和细胞重塑。研究表明转录因子EB核转位（TFEB）在溶酶体生物合成和自噬途径中起着关键作用。（原）肾素受体[（P）RR]是一种多功能蛋白质，在组织肾素-血管紧张素系统的调节中发挥关键作用，并且被认为是液泡H+-ATP酶的重要组成部分，被认为是自噬-溶酶体途径所必需的。基于这些发现，我们推测（P）RR也可能有助于调节饥饿诱导的自噬。在这项研究中，饥饿增加了（P）RR和自噬相关基因的表达，特别是在小鼠的骨骼肌中。在C2 C12小鼠成肌细胞中，饥饿增加了（P）RR表达和TFEB易位，导致自噬相关基因的表达。在饥饿期间，（P）RR的敲低增强了TFEB向细胞核的易位和自噬相关基因的表达。这些结果表明，（P）RR通过影响TFEB的核转位在饥饿诱导的自噬中起缓冲作用。因此，在饥饿期间增加的（P）RR是控制骨骼肌中自噬的重要因素之一。(P)RR可以作为缓冲液，以减少过度的TFEB依赖性自噬通量。
Autophagy is an intracellular catabolic process contributing to the regulation of nutrient homeostasis and cellular remodeling. Studies revealed that the nuclear translocation of transcription factor EB (TFEB) plays a key role in lysosomal biogenesis and autophagic pathways. The (pro)renin receptor [(P)RR] is a multifunctional protein playing a pivotal role in regulation of the tissue renin–angiotensin system and is known as an essential constituent of vacuolar H+‐ATPase, considered to be necessary for the autophagy–lysosome pathway. On the basis of these findings, we postulated that (P)RR may also contribute to the regulation of starvation‐induced autophagy. In this study, starvation increased the expression of (P)RR and autophagy‐related genes, especially, in the skeletal muscles of mice. In C2C12 mouse myoblast cells, starvation increased (P)RR expression and TFEB translocation, leading to the expression of autophagy‐related genes. Knockdown of (P)RR enhanced both the TFEB translocation to the nucleus and the expression of autophagy‐related genes during starvation. These results suggest that (P)RR plays a buffering role in starvation‐induced autophagy by affecting the nuclear translocation of TFEB. Thus, (P)RR, which increases during starvation, is one of the important factors that control autophagy in the skeletal muscles. (P)RR may act as a buffer to reduce excessive TFEB‐dependent autophagy flux.