GrpEL1 regulates mitochondrial unfolded protein response after experimental subarachnoid hemorrhage in vivo and in vitro

Ma, Chao; Gao, Bixi; You, Wanchun; Yu, Zhengquan; Shen, Haitao; Li, Xiang; Li, Haiying; Zhang, Xuwei; Zhong, Wang

doi:10.1016/j.brainresbull.2022.01.014

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…GRPEEL1 is a subtype of the GRPE protein homolog. It acts as a nucleotide exchange factor in mitochondria to influence nonnative protein folding ( Ma et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple Machine Learning Methods Reveal Key Biomarkers of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment

et al. 2022

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Obstructive sleep apnea (OSA) is a worldwide health issue that affects more than 400 million people. Given the limitations inherent in the current conventional diagnosis of OSA based on symptoms report, novel diagnostic approaches are required to complement existing techniques. Recent advances in gene sequencing technology have made it possible to identify a greater number of genes linked to OSA. We identified key genes in OSA and CPAP treatment by screening differentially expressed genes (DEGs) using the Gene Expression Omnibus (GEO) database and employing machine learning algorithms. None of these genes had previously been implicated in OSA. Moreover, a new diagnostic model of OSA was developed, and its diagnostic accuracy was verified in independent datasets. By performing Single Sample Gene Set Enrichment Analysis (ssGSEA) and Counting Relative Subsets of RNA Transcripts (CIBERSORT), we identified possible immunologic mechanisms, which led us to conclude that patients with high OSA risk tend to have elevated inflammation levels that can be brought down by CPAP treatment.

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“…GRPEEL1 is a subtype of the GRPE protein homolog. It acts as a nucleotide exchange factor in mitochondria to influence nonnative protein folding ( Ma et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple Machine Learning Methods Reveal Key Biomarkers of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment

et al. 2022

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“…This implies that ATF5-dependent UPR mt may serve as a regulatory mechanism to dampen the inflammatory response in microglia and potentially mitigate neuroinflammation-associated damage. Xie et al found that the activation of UPR mt attenuated neuroinflammation after ischemic stroke [ 99 ], and in SAH UPR mt regulated the neuronal mitochondrial homeostasis, which decreased the early brain injury [ 100 ].…”

Section: Cross-talk Between Mitochondrial Stress and Neuroinflammatio...mentioning

confidence: 99%

“…A study focusing UPR mt in hemorrhagic stroke showed a mechanism between GrpE like 1, mitochondrial (GrpEL1), a nucleotide exchange factor, and mitochondrial HSP70 (mtHSP70). Although mtHSP70 upregulation was observed in oxyhemoglobin-induced cell model of hemorrhagic stroke, the constitutive binding of GrpEL1 and mtHSP70 was decreased, which resulted in the UPR mt inhibition that contributed to mitochondrial dysfunction and impairment [ 100 ]. Obviously, the sustained pathological condition in neurons contributes to the overaccumulation of mitochondrial stress response.…”

Section: Cross-talk Between Mitochondrial Stress and Neuroinflammatio...mentioning

confidence: 99%

Mitochondrial stress: a key role of neuroinflammation in stroke

Gao,

Peng,

Wang

et al. 2024

J Neuroinflammation

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Stroke is a clinical syndrome characterized by an acute, focal neurological deficit, primarily caused by the occlusion or rupture of cerebral blood vessels. In stroke, neuroinflammation emerges as a pivotal event contributing to neuronal cell death. The occurrence and progression of neuroinflammation entail intricate processes, prominently featuring mitochondrial dysfunction and adaptive responses. Mitochondria, a double membrane-bound organelle are recognized as the “energy workshop” of the body. Brain is particularly vulnerable to mitochondrial disturbances due to its high energy demands from mitochondria-related energy production. The interplay between mitochondria and neuroinflammation plays a significant role in the pathogenesis of stroke. The biological and pathological consequences resulting from mitochondrial stress have substantial implications for cerebral function. Mitochondrial stress serves as an adaptive mechanism aimed at mitigating the stress induced by the import of misfolded proteins, which occurs in response to stroke. This adaptive response involves a reduction in misfolded protein accumulation and overall protein synthesis. The influence of mitochondrial stress on the pathological state of stroke is underscored by its capacity to interact with neuroinflammation. The impact of mitochondrial stress on neuroinflammation varies according to its severity. Moderate mitochondrial stress can bolster cellular adaptive defenses, enabling cells to better withstand detrimental stressors. In contrast, sustained and excessive mitochondrial stress detrimentally affects cellular and tissue integrity. The relationship between neuroinflammation and mitochondrial stress depends on the degree of mitochondrial stress present. Understanding its role in stroke pathogenesis is instrumental in excavating the novel treatment of stroke. This review aims to provide the evaluation of the cross-talk between mitochondrial stress and neuroinflammation within the context of stroke. We aim to reveal how mitochondrial stress affects neuroinflammation environment in stroke.

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“…In mammals, the protein GrpEL1, a nucleotide exchanger that controls the conversion of mtHsp70-ADP to mtHsp70-ATP, is also a regulator of the UPR mt . When this stress response is activated, GrpEL1 forms a complex with mtHsp70 to promote its function and reduce the aggregation of proteins in mitochondria (Ma et al, 2022). Additionally, a recent study suggested that the UPR mt is linked to and dependent on mitophagy, with FUN14 domain-containing protein 1 (FUNDC1) acting upstream of its activation, inducing this stress response by decreasing the mtDNA content (Ji et al, 2022), which increases the misfolded protein load.…”

Section: Upr Mt Regulationmentioning

confidence: 99%

Mitochondrial unfolded protein response (UPRmt): what we know thus far

Torres,

Fleischhart,

Inestrosa

2024

Front. Cell Dev. Biol.

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Mitochondria are key organelles for the optimal function of the cell. Among their many functions, they maintain protein homeostasis through their own proteostatic machinery, which involves proteases and chaperones that regulate protein import and folding inside mitochondria. In the early 2000s, the mitochondrial unfolded protein response (UPRmt) was first described in mammalian cells. This stress response is activated by the accumulation of unfolded/misfolded proteins within the mitochondrial matrix, which results in the transmission of a signal to the nucleus to increase the expression of proteases and chaperones to address the abnormal mitochondrial protein load. After its discovery, this retrograde signaling pathway has also been described in other organisms of different complexities, suggesting that it is a conserved stress response. Although there are some specific differences among organisms, the mechanism of this stress response is mostly similar and involves the transmission of a signal from mitochondria to the nucleus that induces chromatin remodeling to allow the binding of specific transcription factors to the promoters of chaperones and proteases. In the last decade, proteins and signaling pathways that could be involved in the regulation of the UPRmt, including the Wnt signaling pathway, have been described. This minireview aims to summarize what is known about the mechanism of the UPRmt and its regulation, specifically in mammals and C. elegans.

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GrpEL1 regulates mitochondrial unfolded protein response after experimental subarachnoid hemorrhage in vivo and in vitro

Cited by 12 publications

References 47 publications

Multiple Machine Learning Methods Reveal Key Biomarkers of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment

Multiple Machine Learning Methods Reveal Key Biomarkers of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment

Mitochondrial stress: a key role of neuroinflammation in stroke

Mitochondrial unfolded protein response (UPRmt): what we know thus far

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