TY - JOUR
T1 - Autophagy and heat-shock response impair stress granule assembly during cellular senescence
AU - Omer, Amr
AU - Patel, Devang
AU - Moran, Julian Lucas
AU - Lian, Xian Jin
AU - Di Marco, Sergio
AU - Gallouzi, Imed Eddine
N1 - Generated from Scopus record by KAUST IRTS on 2022-09-13
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://linkinghub.elsevier.com/retrieve/pii/S0047637420301780
UR - http://www.scopus.com/inward/record.url?scp=85092742317&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2020.111382
DO - 10.1016/j.mad.2020.111382
M3 - Article
SN - 1872-6216
VL - 192
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
ER -