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Heat shock proteins-driven stress granule dynamics: yet another avenue for cell survival

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Abstract

Heat shock proteins (HSPs) are evolutionary conserved ‘stress-response’ proteins that facilitate cell survival against various adverse conditions. HSP-mediated cytoprotection was hitherto reported to occur principally in two ways. Firstly, HSPs interact directly or indirectly with apoptosis signaling components and suppress apoptosis. Secondly, through chaperon activity, HSPs suppress proteotoxicity and maintain protein-homeostasis. Recent studies highlight the interaction of HSPs with cytoplasmic stress granules (SGs). SGs are conserved cytoplasmic mRNPs granules that aid in cell survival under stressful conditions. We primarily aim to describe the distinct cell survival strategy mediated by HSPs as the crucial regulators of SGs assembly and disassembly. Based on the growing evidence, HSPs and associated co-chaperones act as important determinants of SG assembly, composition and dissolution. Under cellular stress, as a ‘stress-coping mechanism’, the formation of SGs reprograms protein translation machinery and modulates signaling pathways indispensable for cell survival. Besides their role in suppressing apoptosis, HSPs also regulate protein-homeostasis by their chaperone activity as well as by their tight regulation of SG dynamics. The intricate molecular signaling in and around the nexus of HSPs-SGs and its importance in diseases has to be unearthed. These studies have significant implications in the management of chronic diseases such as cancer and neurodegenerative diseases where SGs possess pathological functions.

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Acknowledgements

MS acknowledges the financial support by SERB, New Delhi for the research project (CRG/2020/002009) that led to the conceptualization of the review. AV and MS thank the Head, Prof. Shyam S Chauhan and other faculties of Department of Biotechnology, AIIMS, New Delhi for their kind support. AV acknowledges Department of Biotechnology, Govt. of India for the fellowship. The authors sincerely acknowledge the research groups whose remarkable contributions brought us to the understanding of the emerging role of HSPs in SGs under stress conditions.

Funding

The current work was supported by the research grant from Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi, India (Ref. No. CRG/2020/002009) and AIIMS, Intramural Research Grant (A-830/2020/RS).

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  1. Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Akanksha Verma & Mahendra Seervi

  2. Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala, India

    S. Sumi

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  1. Akanksha Verma
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MS conceived the overall theme and designed the review. MS, AV and SS performed literature search and prepared the manuscript. AV created the schematic diagrams. SS and MS critically reviewed and contributed to the final version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mahendra Seervi.

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Verma, A., Sumi, S. & Seervi, M. Heat shock proteins-driven stress granule dynamics: yet another avenue for cell survival. Apoptosis 26, 371–384 (2021). https://doi.org/10.1007/s10495-021-01678-w

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