The role of the Hippo pathway in autophagy in the heart.
The role of the Hippo pathway in autophagy in the heart.
复制标题
Hippo 通路在心脏自噬中的作用。
DOI：
10.1093/cvr/cvac014
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Sadoshima J.
中科院分区：
文献类型：
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作者：
Maejima Y;Zablocki D;Nah J;Sadoshima J.
Hippo通路是一种进化上保守的信号传导机制，控制着器官大小和肿瘤发生。越来越多的证据表明，自噬是溶酶体介导的细胞降解的重要机制，受Hippo途径调节，从而深刻影响各种细胞类型的细胞生长和死亡反应。在心脏中，Mst 1是Hippo通路的上游组分，不仅诱导细胞凋亡，还通过Beclin 1的磷酸化抑制自噬。雅普/TAZ，转录因子辅因子和Hippo途径的末端效应物，通过TFEB的转录激活影响自噬，TFEB是自噬和溶酶体生物发生的主要调节剂。雅普的细胞丰度由自噬负调控，并且自噬的抑制诱导雅普的积累，其反过来充当诱导自噬体形成的反馈机制。因此，Hippo通路和自噬相互调节，从而深刻影响心肌细胞的存活和死亡。本文综述了Hippo信号通路与自噬的相互作用及其在心脏和心肌细胞应激状态下的功能意义。
The Hippo pathway, an evolutionarily conserved signalling mechanism, controls organ size and tumourigenesis. Increasing lines of evidence suggest that autophagy, an important mechanism of lysosome-mediated cellular degradation, is regulated by the Hippo pathway, which thereby profoundly affects cell growth and death responses in various cell types. In the heart, Mst1, an upstream component of the Hippo pathway, not only induces apoptosis but also inhibits autophagy through phosphorylation of Beclin 1. YAP/TAZ, transcription factor co-factors and the terminal effectors of the Hippo pathway, affect autophagy through transcriptional activation of TFEB, a master regulator of autophagy and lysosomal biogenesis. The cellular abundance of YAP is negatively regulated by autophagy and suppression of autophagy induces accumulation of YAP, which, in turn, acts as a feedback mechanism to induce autophagosome formation. Thus, the Hippo pathway and autophagy regulate each other, thereby profoundly affecting cardiomyocyte survival and death. This review discusses the interaction between the Hippo pathway and autophagy and its functional significance during stress conditions in the heart and the cardiomyocytes therein.