miR-34a-5p regulates PINK1-mediated mitophagy via multiple modes

Tai, Yusi; Pu, M.; Yuan, Luyang; Guo, Huijie; Qiao, Junwen; Lu, Henglei; Wang, Guanghui; Chen, Jing; Qi, Xinming; Tao, Zhouteng; Ren, Jin

doi:10.1016/j.lfs.2021.119415

Cited by 15 publications

(10 citation statements)

References 57 publications

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“…Previous studies showed that miRNAs suppress protein expression by inhibiting translation and promoting mRNA degradation [ 16 ]. The miR-34 family can also alter autophagic flux and suppress cell proliferation [ 17 , 18 , 19 ]. Therefore, we investigated whether miR-34b/c plays a role in the discrepancy between the mRNA and protein levels of Sirt3, PINK1, and Parkin.…”

Section: Resultsmentioning

confidence: 99%

“…Lyu et al found that the age-related generation of miR-29 acts as a key inhibitor during the aging of the H4K20me3, which controls genome stability and promotes cellular senescence [ 26 ]. Other studies reported that the miR-34 family suppresses cancer cell growth by inducing cellular senescence and impeding mitophagy flux via site-specific inhibition [ 17 , 18 , 27 ]. In addition, Aikaterini et al showed that miR-34b and miR-34c contributed to human arterial atherosclerosis and aging by disrupting Sirt1 [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

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IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

et al. 2023

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Endothelial senescence impairs vascular function and thus is a primary event of age-related vasculature diseases. Isocitrate dehydrogenase 2 (IDH2) plays an important role in inducing alpha-ketoglutarate (α-KG) production and preserving mitochondrial function. However, the mechanism and regulation of IDH2 in endothelial senescence have not been elucidated. We demonstrated that downregulation of IDH2 induced accumulation of miR-34b/c, which impaired mitophagy and elevated mitochondrial reactive oxygen species (ROS) levels by inhibiting mitophagy-related markers (PTEN-induced putative kinase 1 (PINK1), Parkin, LC-II/LC3-I, and p62) and attenuating Sirtuin deacetylation 3 (Sirt3) expression. The mitochondrial dysfunction induced by IDH2 deficiency disrupted cell homeostasis and the cell cycle and led to endothelial senescence. However, miR-34b/c inhibition or α-KG supplementation restored Sirt3, PINK1, Parkin, LC-II/LC3-I, p62, and mitochondrial ROS levels, subsequently alleviating endothelial senescence. We showed that IDH2 played a crucial role in regulating endothelial senescence via induction of miR-34b/c in endothelial cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

et al. 2023

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“…Mitophagy represents a selective form of autophagy that cells use to remove dysfunctional or damaged mitochondria. In phosphatase and tensin homolog (PTEN)-induced kinase I/Parkin (PINK1/Parkin)-mediated mitophagy, miR-27a, miR-27b, miR-181a and miR-218 have been shown to regulate PINK1 and Parkin, but newer reports also indicate the involvement of miR-34a-5p, miR-103a-3p and miR-155 [ 252 , 253 , 254 , 255 , 256 ]. In cancer, miR-181a suppresses Parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis [ 257 ].…”

Section: Mirna Regulation Of Mitochondrial Genesmentioning

confidence: 99%

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential

Wagner

Kosnáčová

Chovanec

et al. 2022

IJMS

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Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increasing evidence suggests that mtDNA mutations, mtDNA epigenetics and miRNA regulations dynamically modify signalling pathways in an altered microenvironment, resulting in cancer initiation and progression and aberrant therapy response. In this review, we discuss mitochondria as organelles importantly involved in tumorigenesis and anti-cancer therapy response. Tumour treatment unresponsiveness still represents a serious drawback in current drug therapies. Therefore, studying aspects related to genetic and epigenetic control of mitochondria can open a new field for understanding cancer therapy response. The urgency of finding new therapeutic regimens with better treatment outcomes underlines the targeting of mitochondria as a suitable candidate with new therapeutic potential. Understanding the role of mitochondria and their regulation in cancer development, progression and treatment is essential for the development of new safe and effective mitochondria-based therapeutic regimens.

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“…Yusi Tai et al have demonstrated that PINK1 is a target of miR-34a-5p. miR-34a-5p delays PINK1-mediated autophagic clearance of damaged mitochondria by binding to both 3'-UTR and the Coding DNA sequence (CDS) of PINK1 mRNA through the same non-seed region (28).…”

Section: Mirnas Targeting Pink1mentioning

confidence: 99%

Role of Micrornas in the Pathogenesis of Parkinson's Disease

Hou

Wang

2022

Preprint

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Parkinson’s disease (PD) is a clinically prevalent neurodegenerative disorder mainly affecting the elderly, characterized by loss of dopamine neurons in the substantia nigra. Its main clinical manifestations are motor symptoms such as bradykinesia, resting tremor, rigidity, and postural gait disturbances. Given the complexity and multisystem effects of PD, the exact cause is yet to be elucidated. But multiple mechanisms have been shown to be associated with the pathophysiology of PD, such as the accumulation of α-synuclein, oxidative stress, abnormal apoptosis, and neuroinflammation. MicroRNA (miRNA) is a non-coding single-stranded RNA molecule encoded by endogenous genes. Over the past decade, many studies have reported that miRNA functions in a series of important processes in life process. Moreover, numerous experiments in animal models and clinical investigations have identified miRNA dysregulation in PD and demonstrated that miRNAs play an important role in the development of PD through different pathways. This paper reviews some important miRNAs involved in the development of Parkinson’s disease.

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miR-34a-5p regulates PINK1-mediated mitophagy via multiple modes

Cited by 15 publications

References 57 publications

IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential

Role of Micrornas in the Pathogenesis of Parkinson's Disease

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