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The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis

Significance Statement

Hypoxia, as the main pathological mechanism of these diseases, such as sleep apnea-hypopnea syndrome, ischemic stroke, definitely can induce cellular injury including hippocampal neuronal injury, myocardial cell injury and renal cell injury. Recent studies have found that pathological mechanisms of multi-system injury induced by hypoxia may be associated with autophagy and apoptosis. Autophagy is an intracellular process in which cytoplasmic materials are transported by double-membraned autophagosomes to lysosomes for degradation. With the deepening research of autophagy, researchers found that autophagy plays a dual role in hypoxia-induced cell damage. Apoptosis is an important pathological and physiological mechanism of the multiple system injury induced by hypoxia. Recent studies have shown that autophagy and apoptosis often occur in the same cell, mostly in a sequence in which autophagy precedes apoptosis. There are many common upstream pathways between autophagy and apoptosis. Furthermore, autophagy and apoptosis can regulate each other. The dual role of autophagy may be associated with the regulation of apoptosis. Autophagy could block the induction of apoptosis and attenuate cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cellular injury. While in tumor or cancer cells, studies have demonstrated that the apoptosis has some impacts on the autophagy process. For instance, the activation of apoptosis-related proteins-caspase can degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, which inhibiting autophagy in tumor or cancer cells. Therefore, we discuss and summarize the dual role of autophagy and the interactions and molecular mechanisms between autophagy and apoptosis low-oxygen environments, which is important to understand the mechanism of hypoxic injury.

Figure Legend: Complex interplay between apoptosis and autophagy under hypoxia condition

a: The activation of autophagy induced by hypoxia. b-c: The extrinsic apoptosis and the intrinsic apoptosis induced by hypoxia. d: The accumulation of ROS induced by hypoxia or ischemia could activate pro-apoptotic proteins and then induce apoptosis. e-h: Regulation of apoptosis by autophagy i,j,k: Regulation of autophagy by apoptosis.

The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis. -	. Global Medical Discovery










Journal Reference

Li M, Tan J, Miao Y, Lei P, Zhang Q. Apoptosis. 2015 Jun;20(6):769-77.

Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Anshan Road No. 154, Tianjin, 300052, China.


Hypoxia is one of severe cellular stress and it is well known to be associated with a worse outcome since a lack of oxygen accelerates the induction of apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis caused by hypoxia. Generally autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis-associated caspase which could reduce cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cell damage under hypoxia condition. In addition, the activation of apoptosis-related proteins-caspase can also degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, inhibiting autophagy. Although the relationship between autophagy and apoptosis has been known for rather complex for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This short review discusses and summarizes the dual role of autophagy and the interaction and molecular regulatory mechanisms between autophagy and apoptosis under hypoxia.

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