Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers-New Jersey Medical School, 185 South Orange Ave., MSB G-609, Newark, NJ 07103, USA.
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Cardiovasc Res. 2023 Jan 18;118(17):3320-3330. doi: 10.1093/cvr/cvac014.
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.
Hippo 通路是一种进化上保守的信号转导机制，可控制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 通路调控，从而显著影响各种细胞类型中的细胞生长和死亡反应。在心脏中，Hippo 通路的上游成分 Mst1 不仅通过磷酸化 Beclin 1 诱导细胞凋亡，还抑制自噬。YAP/TAZ，转录因子共激活因子和 Hippo 通路的终效因子，通过转录激活自噬和溶酶体生物发生的主调节因子 TFEB 影响自噬。YAP 的细胞丰度受自噬负调控，自噬抑制诱导 YAP 积累，反过来，YAP 作为反馈机制诱导自噬体形成。因此，Hippo 通路和自噬相互调节，从而显著影响心肌细胞的存活和死亡。本文讨论了 Hippo 通路与自噬之间的相互作用及其在心脏和其中的心肌细胞应激条件下的功能意义。
