Autosomal dominant retinitis pigmentosa-associated gene <i>PRPF8</i> is essential for hypoxia-induced mitophagy through regulating <i>ULK1</i> mRNA splicing

Xu, Guang; Li, Ting; Chen, Jiayi; Li, Chang‐Yan; Zhao, Hongbo; Yao, Chengcheng; Hua, Dong; Wen, Kaiqing; Wang, Kai; Zhao, Jie; Xia, Qing; Zhou, Tao; Zhang, Huafeng; Li, Ailing; Pan, Xin

doi:10.1080/15548627.2018.1501251

Cited by 45 publications

(37 citation statements)

References 78 publications

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“…In addition, the resistance of mt-Keima to lysosomal degradation causes the integration of the mt-Keima signal, allowing for the easy quantitative measurement of mitophagy activity. These properties have led to the increasing use of mt-Keima to study mitophagy in vitro (13)(14)(15)(16). We previously generated a transgenic mouse that ubiquitously expresses the mt-Keima protein, allowing the first general observation of in vivo mitophagy (17).…”

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confidence: 99%

Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo

Kim

Yoon

et al. 2019

FASEB j.

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Mitophagy has been implicated in mitochondrial quality control and in various human diseases. However, the study of in vivo mitophagy remains limited. We previously explored in vivo mitophagy using a transgenic mouse expressing the mitochondria‐targeted fluorescent protein Keima (mt‐Keima). Here, we generated mt‐Keima Drosophila to extend our efforts to study mitophagy in vivo. A series of experiments confirmed that mitophagy can be faithfully and quantitatively measured in mt‐Keima Drosophila. We also showed that alterations in mitophagy upon environmental and genetic perturbation can be measured in mt‐Keima Drosophila. Analysis of different tissues revealed a variation in basal mitophagy levels in Drosophila tissues. In addition, we found a significant increase in mitophagy levels during Drosophila embryogenesis. Importantly, loss‐of‐function genetic analysis demonstrated that the phosphatase and tensin homolog‐induced putative kinase 1 (PINK1)‐Parkin pathway is essential for the induction of mitophagy in vivo in response to hypoxic exposure and rotenone treatment. These studies showed that the mt‐Keima Drosophila system is a useful tool for understanding the role and molecular mechanism of mitophagy in vivo. In addition, we demonstrated the essential role of the PINK1‐Parkin pathway in mitophagy induction in response to mitochondrial dysfunction.—Kim, Y. Y., Um, J.‐H., Yoon, J.‐H., Kim, H., Lee, D.‐Y., Lee, Y. J., Jee, H. J., Kim, Y. M., Jang, J. S., Jang, Y.‐G., Chung, J., Park, H. T., Finkel, T., Koh, H., Yun, J. Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo. FASEB J. 33, 9742–9751 (2019). http://www.fasebj.org

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confidence: 99%

Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo

Kim

Yoon

et al. 2019

FASEB j.

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“…PRPF8 is the core protein of splicing, the mutation of PRPF8 could cause the death of model cell, and it has an important relationship with the occurrence of the disease particularly in cancer [21]. Recent study reported that knockdown of PRPF8 signi cantly impairs mitophagosome formation, thus, these ndings demonstrate that PRPF8 is essential for mitophagy and suggest that dysregulation of spliceosome-mediated mitophagy may contribute to pathogenesis of disease such as cancer [22]. PRPF8 is a highly conserved pre-mRNA splicing factor and a component of spliceosomal small nuclear ribonucleoproteins (snRNPs), which is essential in RNA and mRNA splicing through transesteri cation and spliceosome processes [23].…”

Section: Discussionmentioning

confidence: 99%

circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

Deng

et al. 2020

Preprint

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Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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“…When mitochondria are damaged, they can be selectively removed by autophagy, called mitophagy. Some genes associated with autosomal dominant RP, including PRPF6, PRPF31, SNRNP200, and PRPF8 (core spliceosomal components) [129][130][131], are suggested to be responsible for ULK1 mRNA mis-splicing (an important protein for mitophagy initiation) and subsequent mitophagy defects [132].…”

Section: Inherited Retinal Dystrophiesmentioning

confidence: 99%

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

et al. 2020

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Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich's ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsies. Despite the discrimination between cause and effect may not be easy on many occasions, all these conditions are Mendelian rare diseases that share oxidative stress as a common factor, and this may represent a potential target for therapies.

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Autosomal dominant retinitis pigmentosa-associated gene PRPF8 is essential for hypoxia-induced mitophagy through regulating ULK1 mRNA splicing

Cited by 45 publications

References 78 publications

Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo

Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo

circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

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