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Autophagy and apoptosis: where do they meet?

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Abstract

Autophagy and apoptosis are two important cellular processes with complex and intersecting protein networks; as such, they have been the subjects of intense investigation. Recent advances have elucidated the key players and their molecular circuitry. For instance, the discovery of Beclin-1’s interacting partners has resulted in the identification of Bcl-2 as a central regulator of autophagy and apoptosis, which functions by interacting with both Beclin-1 and Bax/Bak respectively. When localized to the endoplasmic reticulum and mitochondria, Bcl-2 inhibits autophagy. Cellular stress causes the displacement of Bcl-2 from Beclin-1 and Bax, thereby triggering autophagy and apoptosis, respectively. The induction of autophagy or apoptosis results in disruption of complexes by BH3-only proteins and through post-translational modification. The mechanisms linking autophagy and apoptosis are not fully defined; however, recent discoveries have revealed that several apoptotic proteins (e.g., PUMA, Noxa, Nix, Bax, XIAP, and Bim) modulate autophagy. Moreover, autophagic proteins that control nucleation and elongation regulate intrinsic apoptosis through calpain- and caspase-mediated cleavage of autophagy-related proteins, which switches the cellular program from autophagy to apoptosis. Similarly, several autophagic proteins are implicated in extrinsic apoptosis. This highlights a dual cellular role for autophagy. On one hand, autophagy degrades damaged mitochondria and caspases, and on the other hand, it provides a membrane-based intracellular platform for caspase processing in the regulation of apoptosis. In this review, we highlight the crucial factors governing the crosstalk between autophagy and apoptosis and describe the mechanisms controlling cell survival and cell death.

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Acknowledgments

We thank National Institute of Technology, Rourkela for providing facility for this research work. Research support was provided to SKB in part by Rapid Grant for Young Investigator (RGYI) award, Department of Biotechnology, Government of India and Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India.

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The authors declare that they have no conflict of interest.

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  1. Department of Life Science, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India

    Subhadip Mukhopadhyay, Prashanta Kumar Panda, Niharika Sinha, Durgesh Nandini Das & Sujit Kumar Bhutia

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  1. Subhadip Mukhopadhyay
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  2. Prashanta Kumar Panda
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Correspondence to Sujit Kumar Bhutia.

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Subhadip Mukhopadhyay and Prashanta Kumar Panda have contributed equally to this work.

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Mukhopadhyay, S., Panda, P.K., Sinha, N. et al. Autophagy and apoptosis: where do they meet?. Apoptosis 19, 555–566 (2014). https://doi.org/10.1007/s10495-014-0967-2

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