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Caspases: A Molecular Switch Node in the Crosstalk between Autophagy and Apoptosis
Authors:Haijian Wu  Xiaoru Che  Qiaoli Zheng  An Wu  Kun Pan  Anwen Shao  Qun Wu  Jianmin Zhang  Yuan Hong
Institution:1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;;2. Department of Cardiology, Zhejiang Provincial People''s Hospital, Hangzhou, China;;3. Clinical Research Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.;4. Department of Neurological Surgery, Weill Cornell Medical College, New York, New York, USA.
Abstract:Autophagy and apoptosis are two important catabolic processes contributing to the maintenance of cellular and tissue homeostasis. Autophagy controls the turnover of protein aggregates and damaged organelles within cells, while apoptosis is the principal mechanism by which unwanted cells are dismantled and eliminated from organisms. Despite marked differences between these two pathways, they are highly interconnected in determining the fate of cells. Intriguingly, caspases, the primary drivers of apoptotic cell death, play a critical role in mediating the complex crosstalk between autophagy and apoptosis. Pro-apoptotic signals can converge to activate caspases to execute apoptotic cell death. In addition, activated caspases can degrade autophagy proteins (i.e., Beclin-1, Atg5, and Atg7) to shut down the autophagic response. Moreover, caspases can convert pro-autophagic proteins into pro-apoptotic proteints to trigger apoptotic cell death instead. It is clear that caspases are important in both apoptosis and autophagy, thus a detailed deciphering of the role of caspases in these two processes is still required to clarify the functional relationship between them. In this article, we provide a current overview of caspases in its interplay between autophagy and apoptosis. We emphasized that defining the role of caspases in autophagy-apoptosis crosstalk will provide a framework for more precise manipulation of these two processes during cell death.
Keywords:autophagy  apoptosis  caspases  Atg proteins  crosstalk  cell death  
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