Vimentin protects differentiating stem cells from stress

Pattabiraman, Sundararaghavan; Azad, Gajendra Kumar; Amen, Triana; Brielle, Shlomi; Park, Jung Eun; Sze, Siu Kwan; Meshorer, Eran; Kaganovich, Daniel

doi:10.1038/s41598-020-76076-4

Cited by 41 publications

(29 citation statements)

References 69 publications

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“…SG-dependent VDAC clustering demonstrates how SG signaling pathways can induce multi-tiered architectural changes in the cell, affecting metabolism and cellular fate. As recent findings suggest, SG can form on the surface of membrane-bound organelles or cytoskeletal components regulating cellular functions such as kinase signaling, altering local translation ( Cioni et al., 2019 ; Lee et al., 2020 ; Liao et al., 2019 ; Lin et al., 2016 ; Pattabiraman et al., 2020 ); herein, we show that SGs regulate mitochondrial function by altering local permeability.…”

Section: Discussionsupporting

confidence: 62%

“…First, we asked whether starvation-induced SGs associate with membrane-bound organelles responsible for metabolic regulation (ER, mitochondria, LDs, Golgi, and peroxisomes) ( Haimovich et al., 2016 ). This idea is not unprecedented, as SGs have recently been reported to make physical contacts with the ER, lysosomes, cytoskeletal elements, and membrane-bound compartments ( Cioni et al., 2019 ; Lee et al., 2020 ; Liao et al., 2019 ; Lin et al., 2016 ; Amen and Kaganovich, 2020b ; Pattabiraman et al., 2020 ). We examined SG association with membrane-bound compartments following 9 h of fuel depletion, when SGs first appear ( Figures 2 A and S4 A).…”

Section: Resultsmentioning

confidence: 99%

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Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability

Amen

Kaganovich

2021

Cell Reports

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Summary The formation of stress granules (SGs) is an essential aspect of the cellular response to many kinds of stress, but its adaptive role is far from clear. SG dysfunction is implicated in aging-onset neurodegenerative diseases, prompting interest in their physiological function. Here, we report that during starvation stress, SGs interact with mitochondria and regulate metabolic remodeling. We show that SG formation leads to a downregulation of fatty acid β-oxidation (FAO) through the modulation of mitochondrial voltage-dependent anion channels (VDACs), which import fatty acids (FAs) into mitochondria. The subsequent decrease in FAO during long-term starvation reduces oxidative damage and rations FAs for longer use. Failure to form SGs, whether caused by the genetic deletion of SG components or an amyotrophic lateral sclerosis (ALS)-associated mutation, translates into an inability to downregulate FAO. Because metabolic dysfunction is a common pathological element of neurodegenerative diseases, including ALS, our findings provide a direction for studying the clinical relevance of SGs.

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Section: Discussionsupporting

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability

Amen

Kaganovich

2021

Cell Reports

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“…Moreover, the absence of vimentin impairs spontaneous in vitro differentiation of ES cells to the endothelial phenotype [ 12 ]. A recent report also suggests that vimentin intervenes in the stress response of differentiating cells [ 96 ].…”

Section: Discussionmentioning

confidence: 99%

Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells

et al. 2022

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Background The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive. Results We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role. Conclusions Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.

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“…This cytoskeleton protein plays a pivotal role in maintaining the shape and integrity of cells. It is also notable that vimentin is crucial for tissue homeostasis, protecting cells from protein misfolding stress [45]. Given the above, the Eca EPCs OB show features of early apoptotic cells with decreased cellular function, including self-renewal potential.…”

Section: Discussionmentioning

confidence: 99%

Obesity affects mitochondrial metabolism and proliferative potential of equine endometrial progenitor cells

Śmieszek

Marcinkowska

Pielok

et al. 2021

Preprint

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The study aimed to investigate the influence of obesity on cellular features of equine endometrial progenitor cells (Eca EPCs), including viability, proliferation capacity, mitochondrial metabolism, and oxidative homeostasis. Eca EPCs derived from non-obese (Non-OB) and obese (OB) mares were characterised by cellular phenotype and multipotency.Obesity-induced changes in the activity of Eca EPCs include the decline of their proliferative activity, clonogenic potential, mitochondrial metabolism and enhanced oxidative stress. Eca EPCs isolated from obese mares were characterised by an increased occurrence of early apoptosis, loss of mitochondrial dynamics, and senescence-associated phenotype. Attenuated metabolism of Eca EPCs OB was related to increased expression of pro-apoptotic markers (CASP9, BAX, P53, P21), enhanced expression of OPN, PI3K and AKT, simultaneously with decreased signalling stabilising cellular homeostasis (including mitofusin, SIRT1, FOXP3).Obesity alters functional features and self-renewal potential of endometrial progenitor cells. The impaired cytophysiology of progenitor cells from obese endometrium predict lower regenerative capacity if used as autologous transplants.

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Vimentin protects differentiating stem cells from stress

Cited by 41 publications

References 69 publications

Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability

Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability

Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells

Obesity affects mitochondrial metabolism and proliferative potential of equine endometrial progenitor cells

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