The Hippo Pathway Orchestrates Mitochondrial Quality Control: A Novel Focus on Cardiovascular Diseases
Ying Tan, Lei Cai, Huifang Tang, Xiao Zhu, Guanghui Yi
Abstract
Mitochondria serve as a hub for cell metabolism, energy production, and reactive oxygen species generation through multiple signaling pathways that control cardiomyocyte survival and death and contribute to the pathophysiological process of cardiovascular diseases (CVDs). Therefore, maintaining mitochondrial quality control (MQC) is essential for mitochondrial homeostasis and cardiac health. The Hippo pathway is a conserved signaling cascade that regulates mitochondrial function and cardiomyocyte fate and plays a crucial role in cardiac regeneration, repair, and diseases. MQC and the Hippo pathway are tightly coupled in CVDs, and several regulatory elements of the Hippo pathway directly/indirectly regulate mitochondria-related proteins to mediate mitochondrial morphology and function. In turn, mitochondrial morphology partly influences Hippo pathway function in the heart. This review outlines the underlying mechanisms by which the Hippo pathway regulates MQC from a variety of perspectives, including mitochondrial dynamics, mitophagy, mitochondrial biogenesis, mitochondrial apoptosis under oxidative stress, and mitochondrial metabolism. We also discuss the roles of the Hippo pathway in orchestrating mitochondria in CVDs, such as myocardial ischemia-reperfusion injury, septic cardiomyopathy, and diabetic cardiomyopathy, which may provide a novel therapeutic strategy.