Emerging views of OPTN (optineurin) function in the autophagic process associated with disease

Qiu, Yueping; Wang, Jincheng; Yang, Bo; Wang, Jiajia; He, Qiaojun; Weng, Qinjie

doi:10.1080/15548627.2021.1908722

Cited by 65 publications

(49 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it is worth clarifying further that mitophagy has different types of activation, including PINK1/Parkin and receptor-induced mitophagy such as NIX, BNIP3, FUNDC1 [ 55 ]. We only examined PINK1/Parkin, which has a close relationship with osteoporosis [ 44 , 56 ]. Due to the limited scope of this study, we were unable to include other types of mitophagy activation, and studies on receptor-induced mitophagy on osteoporosis are lacking, which needs to be further work in the future.…”

Section: Discussionmentioning

confidence: 99%

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway

Zhao

Peng

Wang

et al. 2022

Cells

View full text Add to dashboard Cite

Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H2O2 stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 μM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway

Zhao

Peng

Wang

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Mitophagy is a complex process and PINK1 accumulates in the outer membrane of depolarized mitochondria and takes up the cytosolic ubiquitin ligase PARKIN and phosphorylates both PARKIN and ubiquitin (21) . Activated PARKIN, in turn, ubiquitinates the scores of mitochondrial outer membrane proteins of depolarized mitochondria and subsequent recruitment of multiple autophagy cargo adapters such as OPTN and NDP52 (22) . Finally, all these cargoes directly bind to LC3 in the autophagosome leading to the degradation of all mitochondria in autophagosomes (23) .…”

Section: Discussionmentioning

confidence: 99%

Mitophagy in the A549 lung cancer cell line, radiation-induced damage, and the effect of ATM and PARKIN on the mitochondria

et al. 2022

View full text Add to dashboard Cite

Background: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer, and radiotherapy (RT) is used for the cancer therapy. RT affects DNA and causes DNA double-strand breaks which are repaired by DNA repair protein ataxia telangiectasia mutated (ATM). RT also affects the mitochondria which is a key player in mediating the radiation response in tumors and removing damaged mitochondria through mitophagy. During mitophagy, PARKIN accumulates on defective mitochondria to mediate the clearance of damaged mitochondria. This study examines the effect of radiation on mitophagy using PARKIN and ATM antibodies on the human NSCLC A549 line. Materials and Methods: A549 cells were treated with 2, 4, 6 and 8 Gy of radiation were analyzed on days 1 and 3 after a single dose of radiotherapy. PARKIN and ATM expressions of A549 cells were examined by using immunohistochemical technique. Results: In the control groups, weak immunoreactivity of ATM and PARKIN was observed on both days 1 and 3. The most intense ATM expression was seen in the 6 and 8 Gy groups after day 1. The most intense PARKIN expression was seen after the days 1 and 3 in the 2 Gy groups. PARKIN immunoreactivity decreased due to increasing radiation dose. Conclusion: It must be considered that mitophagy mechanisms are activated in RT applications. It must be considered that the activation of mitophagy mechanisms in RT and A549 lung cancer cell lines may provide hemostasis in cancer cells. Molecules targeting mitophagy must be developed for use with radiotherapy.

show abstract

“…OPTN, the most recently identified autophagy receptor, was initially named because it corresponds to one of the genes encoding the glaucoma form of the "optic neuropathy inducing" protein [10]. OPTN has been implicated genetically in many human diseases, such as glaucoma, Paget's disease and amyotrophic lateral sclerosis (ALS) [11]. In the retina, OPTN is preferentially expressed in RGCs [12].…”

Section: Introductionmentioning

confidence: 99%

Sirt5-mediated desuccinylation of OPTN protects retinal ganglion cells from autophagic flux blockade in diabetic retinopathy

et al. 2022

View full text Add to dashboard Cite

Retinal neurodegeneration develops early in the course of diabetic retinopathy (DR), and our previous research showed that succinate accumulation results in retinal ganglion cells (RGCs) dysfunction in the retinas of rats with DR. Succinate can enhance lysine succinylation, but the succinylation of DR is not well understood. In this study, we investigated the role of the succinylome in DR and identified the key factor in this process. TMT labeling and LC–MS/MS analysis were combined to quantify the differentially succinylated proteins between vitreous humor (VH) samples from DR and non-DR patients. A total of 74 sites in 35 proteins were differentially succinylated between DR and non-DR vitreous humor samples, among which succinylation of the K108 site of optineurin (OPTN K108su) in the defense response was enriched by GO analysis based on the biological process category. Then, using a streptozotocin (STZ)-induced diabetic rat model, R28 cells and primary rat RGCs (rRGCs), we demonstrated that OPTN underwent lysine succinylation in the retinas of rats with DR and that OPTN K108su mediated autophagic flux blockade under high-glucose (HG) conditions. Sirt5 can desuccinylate OPTN K108su, thus protecting RGCs function from high glucose-induced RGCs autophagic flux blockade in the diabetic retina. Overall, desuccinylation of OPTN is an essential adaptive mechanism for ameliorating autophagic flux blockade in RGCs under DR conditions, and targeting the Sirt5-desuccK108-OPTN axis may thus open an avenue for therapeutic intervention in RCGs dysfunction.

show abstract

Emerging views of OPTN (optineurin) function in the autophagic process associated with disease

Cited by 65 publications

References 140 publications

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway

Mitophagy in the A549 lung cancer cell line, radiation-induced damage, and the effect of ATM and PARKIN on the mitochondria

Sirt5-mediated desuccinylation of OPTN protects retinal ganglion cells from autophagic flux blockade in diabetic retinopathy

Contact Info

Product

Resources

About