Autophagy and heat-shock response impair stress granule assembly during cellular senescence

• Published in: Mechanisms of ageing and development Vol. 192; p. 111382
• Main Authors: Omer, Amr, Patel, Devang, Moran, Julian Lucas, Lian, Xian Jin, Di Marco, Sergio, Gallouzi, Imed-Eddine
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2020
• Subjects: Ageing; Cellular senescence; Molecular biology; Oxidative stress; Stress granules; Oxidative stress; Molecular biology; Stress granules; Ageing; Cellular senescence
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2020.111382

•Senescent cells are unable to form stress granules correlating with an upregulation in the heat-shock response and autophagy.•Depletion of HSP70 or ATG5 restores stress granule assembly during senescence under chronic oxidative stress conditions.•However, depletion of HSP70 or ATG5 did not affect the clearance of stress granules during recovery from chronic stress.•Senescent cells display unique heat-shock and autophagy-dependent ability to impair the chronic formation of stress granules. Stress granules (SGs) are membraneless organelles formed in response to insult. These granules are related to pathological granules found in age-related neurogenerative diseases such as Parkinson’s and Alzheimer’s. Previously, we demonstrated that senescent cells, which accumulate with age, exposed to chronic oxidative stress, are unable to form SGs. Here, we show that the senescent cells’ inability to form SGs correlates with an upregulation in both the heat-shock response and autophagy pathways, both of which are well-established promoters of SG disassembly. Our data also reveals that the knockdown of HSP70 and ATG5, important components of the heat-shock response and autophagy pathways, respectively, restores the number of SGs formed in senescent cells exposed to chronic oxidative stress. Surprisingly, under these conditions, the depletion of HSP70 or ATG5 did not affect the clearance of these SGs during their recovery from chronic stress. These data reveal that senescent cells possess a unique heat-shock and autophagy-dependent ability to impair the formation of SGs in response to chronic stress, thereby expanding the existing understanding of SG dynamics in senescent cells and their potential contribution to age-related neurodegenerative diseases.