mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases

Sandoval, Marti Cadena; Heberle, Alexander Martin; Rehbein, Ulrike; Barile, Cecilia; Pittol, José M. Ramos; Thedieck, Kathrin

doi:10.3389/fragi.2021.761333

Cited by 9 publications

(10 citation statements)

References 211 publications

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“…Although DAB2 expression can be regulated by other miRNAs, like miR‐93 and miR‐191, 43,44 its relationship with SA‐miRNAs has not been reported before. In a matter of speaking, several pieces of information are supportive for our finding, which demonstrated the implication of DAB2 in AKT–mTOR pathway regulation, 33 or the aging‐promoting implication of consistent mTOR activation 45,46 . Moreover, the association between DAB2 and autophagy has been reported in previous.…”

Section: Discussionsupporting

confidence: 87%

“…In a matter of speaking, several pieces of information are supportive for our finding, which demonstrated the implication of DAB2 in AKT-mTOR pathway regulation, 33 or the aging-promoting implication of consistent mTOR activation. 45,46 Moreover, the association between DAB2 and autophagy has been reported in previous. The relevant stated that DAB2 can obstruct the formation of the BECLIN-1-VPS34 complex and subsequently inhibit autophagy processes.…”

Section: Discussionmentioning

confidence: 65%

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AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation

Zhang,

Gong,

Zhao

et al. 2024

MedComm

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Senescence‐associated microRNAs (SA‐miRNAs) are important molecules for aging regulation. While many aging‐promoting SA‐miRNAs have been identified, confirmed aging‐suppressive SA‐miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR‐708 expression is decreased in senescent cells and aged tissues and revealed that miR‐708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR‐708, we unraveled that miR‐708 directly targets the 3′UTR of the disabled 2 (Dab2) gene and inhibits the expression of DAB2. Interestingly, miR‐708‐caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP‐activated protein kinase (AMPK) activation can upregulate miR‐708 via the elevation of DICER expression, and miR‐708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR‐708 as an aging‐suppressive SA‐miRNA for the first time and uncovered a new signaling cascade, in which miR‐708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR‐708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 65%

AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation

Zhang,

Gong,

Zhao

et al. 2024

MedComm

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“…SGs are membrane-less dense messenger ribonucleoprotein (mRNP) particles formed in the cytoplasm, containing polyadenylated mRNAs forced to suspend translation due to the stress [ 55 ], small ribosomal subunits (40S), translation initiation factor PABP, and RNA binding protein TIA/1R. Similarly, several non-RNA-binding proteins such as signal transduction proteins are also contained in SGs [ 56 ]; however, RNAs whose translation is induced by stress are not included in the SGs [ 57 ].…”

Section: Antioxidant Mechanisms In Oocytesmentioning

confidence: 99%

Oxidative Stress and Oocyte Cryopreservation: Recent Advances in Mitigation Strategies Involving Antioxidants

Cao

Qin

Pan

et al. 2022

Cells

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Oocyte cryopreservation is widely used in assisted-reproductive technology and animal production. However, cryopreservation not only induces a massive accumulation of reactive oxygen species (ROS) in oocytes, but also leads to oxidative-stress-inflicted damage to mitochondria and the endoplasmic reticulum. These stresses lead to damage to the spindle, DNA, proteins, and lipids, ultimately reducing the developmental potential of oocytes both in vitro and in vivo. Although oocytes can mitigate oxidative stress via intrinsic antioxidant systems, the formation of ribonucleoprotein granules, mitophagy, and the cryopreservation-inflicted oxidative damage cannot be completely eliminated. Therefore, exogenous antioxidants such as melatonin and resveratrol are widely used in oocyte cryopreservation to reduce oxidative damage through direct or indirect scavenging of ROS. In this review, we discuss analysis of various oxidative stresses induced by oocyte cryopreservation, the impact of antioxidants against oxidative damage, and their underlying mechanisms. We hope that this literature review can provide a reference for improving the efficiency of oocyte cryopreservation.

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“…However, it is unclear whether SGs formation mediated by the eIF4E-4EBP complex depends on mTORC1 inactivation. Currently, there is no experimental evidence to show that mTOR inhibition is sufficient to induce SGs formation ( 21 , 22 ). Although it is somewhat paradoxical, there is growing evidence showing that mTORC1 is required for the formation of SGs ( 21 , 23 , 24 ).…”

Section: Signaling Pathways For Sgs Assemblymentioning

confidence: 99%

Stress granules dynamics: benefits in cancer

Lee

Namkoong

2022

BMB Rep

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Stress granules (SGs) are stress-induced subcellular compartments, which carry out a particular function to cope with stress. These granules protect cells from stress-related damage and cell death through dynamic sequestration of numerous ribonucleoproteins (RNPs) and signaling proteins, thereby promoting cell survival under both physiological and pathological condition. During tumorigenesis, cancer cells are repeatedly exposed to diverse stress stimuli from the tumor microenvironment, and the dynamics of SGs is often modulated due to the alteration of gene expression patterns in cancer cells, leading to tumor progression as well as resistance to anticancer treatment. In this mini review, we provide a brief discussion about our current understanding of the fundamental roles of SGs during physiological stress and the effect of dysregulated SGs on cancer cell fitness and cancer therapy. [

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mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases

Cited by 9 publications

References 211 publications

AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation

AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation

Oxidative Stress and Oocyte Cryopreservation: Recent Advances in Mitigation Strategies Involving Antioxidants

Stress granules dynamics: benefits in cancer

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