SIRT1 alleviates high-magnitude compression-induced senescence in nucleus pulposus cells via PINK1-dependent mitophagy

Wang, Yiyang; Wang, Haoming; Zhuo, Yunyun; Hu, Yanzhu; Zhang, Zetong; Ye, Jixing; Liu, Liehua; Luo, Lei; Zhao, Chen; Zhou, Qiang; Li, Pei

doi:10.18632/aging.103587

Cited by 38 publications

(39 citation statements)

References 46 publications

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“…In addition to maintaining cellular homeostasis, autophagy eliminates damaged organelles for cellular quality control purposes. Notably, damaged mitochondria can be eliminated through the mitophagy pathway to maintain mitochondrial homeostasis, energy production, and neuronal survival ( Wang and Wang, 2019 ; Wang et al, 2020 ). In other words, mitophagy dysfunction can result in the accumulation of damaged mitochondria, which in turn is associated with a various neurological pathological conditions ( Yang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…PINK1-mediated mitophagy is currently the most well-established way mediate mitophagy in mammalian cells ( Youle and Narendra, 2011 ). Depletion of PINK1, a key mitophagic regulator, impaired mitophagy and blocked the protective role of Sirt1 against compression induced senescence in nucleus pulposus cells ( Wang et al, 2020 ). In our study, we showed that increased level of PINK1 protein after Sirt1 activator RSV treatment in isolated mitochondrial protein.…”

Section: Discussionmentioning

confidence: 99%

“…Sirt1, best-studied member of the sirtuin family, is a critical regulator of autophagy ( Tang, 2016 ). Recently, studies have shown that Sirt1 is vital for the disposal of defective mitochondria by mitophagy ( Fang, 2019 ; Wang et al, 2020 ). In mice, environmental stresses reportedly can activate Sirt1 and lead to NTD-like phenotypes ( Li et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

Zhao

Liú

et al. 2021

Front. Cell Dev. Biol.

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Neural tube defects (NTDs) are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Mitophagy is the best-known way of mitochondrial quality control. However, the role and regulation of mitophagy in NTDs have not yet been elucidated. In this study, we used an all-trans retinoic acid (ATRA)-induced rat model to investigate mitophagy and its underlying mechanism in spina bifida aperta (SBA). The results of western blot, immunofluorescence and RT-qPCR analyses indicated that mitophagy was impaired and Sirt1 was downregulated in SBA. Administration of resveratrol-a strong specific Sirt1 activator-activated Sirt1, thus attenuating autophagy suppression and ameliorating SBA. RNA-sequencing and bioinformatics analysis results indicated that transcriptional regulation played an important role in NTDs. A luciferase reporter assay was performed to demonstrate that the transcription factor Bhlhe40 directly bound to and negatively regulated Sirt1 expression. Further, we discovered that the Bhlhe40/Sirt1 axis regulated mitophagy in neural stem cells. Collectively, our results for the first time demonstrate that Bhlhe40/Sirt1 axis regulated mitophagy is implicated in ATRA-induced SBA. Our findings provide new insights into pathogenesis of NTDs and a basis for potential therapeutic targets for NTDs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

Zhao

Liú

et al. 2021

Front. Cell Dev. Biol.

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“…However, the role of this modification in the pathogenesis of IVDD is fully mysterious. Additionally, the silent mating type information regulator 2 homolog-1 (SIRT1) played a protective role in IVDD and preserves the normal NP cell phenotype ( Zhang et al, 2011 ; Feng et al, 2016 ; Wang Y. et al, 2020 ). The mechanism behind has not been explicated yet.…”

Section: Introductionmentioning

confidence: 99%

N6-Methyladenosine Induced miR-34a-5p Promotes TNF-α-Induced Nucleus Pulposus Cell Senescence by Targeting SIRT1

Zhu

Sun

Zhu

et al. 2021

Front. Cell Dev. Biol.

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Low back pain is tightly associated with intervertebral disc degeneration (IVDD) and aberrant nucleus pulposus (NP) is a critical cause. miRNAs N6-methyladenosine (m6A) modification accounts for the TNF-α-induced senescence of NP cells. The aim of this study was to investigate whether m6A modification regulates TNF-α-mediated cell viability, cell cycle arrest, and cell senescence and how it works. The results showed that METTL14 expression positively correlated with m6A and TNF-α expression in HNPCs. The knockdown of METTL14 led to the inhibition of the TNF-α-induced cell senescence. METTL14 overexpression promoted cell senescence. METTL14 regulated the m6A modification of miR-34a-5p and interacted with DGCR8 to process miR-34a-5p. The miR-34a-5p inhibitor inhibited the cell cycle senescence of HNPCs. miR-34a-5p was predicted to interact with the SIRT1 mRNA. SIRT1 overexpression counteracted the miR-34a-5p-promoted cell senescence. METTL14 participates in the TNF-α-induced m6A modification of miR-34a-5p to promote cell senescence in HNPCs and NP cells of IVDD patients. Downregulation of either METTL14 expression or miR-34a-5p leads to the inhibition of cell cycle arrest and senescence. SIRT1 mRNA is an effective binding target of miR-34a-5p, and SIRT1 overexpression mitigates the cell cycle arrest and senescence caused by miR-34a-5p.

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“…In addition to maintaining cellular homeostasis, autophagy eliminates damaged organelles for cellular quality control purposes. Notably, damaged mitochondria can be eliminated through the mitophagy pathway to maintain mitochondrial homeostasis, energy production, and neuronal survival Wang et al, 2020). In other words, mitophagy dysfunction can result in the accumulation of damaged mitochondria, which in turn is associated with a various neurological pathological conditions (Yang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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SIRT1 alleviates high-magnitude compression-induced senescence in nucleus pulposus cells via PINK1-dependent mitophagy

Cited by 38 publications

References 46 publications

Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

N6-Methyladenosine Induced miR-34a-5p Promotes TNF-α-Induced Nucleus Pulposus Cell Senescence by Targeting SIRT1

Table_1.XLS

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