PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis

Sarraf, Shireen A.; Sideris, Dionisia P.; Γιαγτζόγλου, Νικόλαος; Ni, Lina; Kankel, Mark W.; Sen, Anindya; Bochicchio, Lauren E.; Huang, Chiu-Hui; Nussenzweig, Samuel C.; Worley, Stuart H.; Morton, Paul D.; Artavanis‐Tsakonas, Spyros; Youle, Richard J.; Pickrell, Alicia M.

doi:10.1016/j.celrep.2019.08.085

Cited by 74 publications

(86 citation statements)

References 58 publications

(84 reference statements)

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“…With regard to TBK1, it has been proven that TBK1 takes part in modulating cell growth and autophagy [43]. Moreover, Sarraf et al [44] also indicated that TBK1 exerted an important role in mitophagy.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of autophagy-related genes within esophageal carcinoma

Chen

Cao

et al. 2020

BMC Cancer

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Background: Several works suggest the importance of autophagy during esophageal carcinoma development. The aim of the study is to construct a scoring system according to the expression profiles of major autophagy-related genes (ARGs) among esophageal carcinoma cases. Methods: The Cancer Genome Atlas was employed to obtain the esophageal carcinoma data. Thereafter, the online database Oncolnc (http://www.oncolnc.org/) was employed to verify the accuracy of our results. According to our results, the included ARGs were related to overall survival (OS). Results: We detected the expression patterns of ARG within esophageal carcinoma and normal esophageal tissues. In addition, we identified the autophagy related gene set, including 14 genes displaying remarkable significance in predicting the esophageal carcinoma prognosis. The cox regression results showed that, 7 ARGs (including TBK1, ATG5, HSP90AB1, VAMP7, DNAJB1, GABARAPL2, and MAP2K7) were screened to calculate the ARGs scores. Typically, patients with higher ARGs scores were associated with poorer OS. Moreover, the receiver operating characteristic (ROC) curve analysis suggested that, ARGs accurately distinguished the healthy people from esophageal carcinoma patients, with the area under curve (AUC) value of > 0.6. Conclusion: A scoring system is constructed in this study based on the main ARGs, which accurately predicts the outcomes for esophageal carcinoma.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of autophagy-related genes within esophageal carcinoma

Chen

Cao

et al. 2020

BMC Cancer

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“…Increased risk for Parkinson's disease has been associated with mutations in SNCA, PARK2 (parkin), PINK1, DJ-1, and LRRK2 which have been linked to mitochondrial function and oxidative stress (Yan et al, 2012). PINK1 and parkin mediates clearance of damaged mitochondria by mitophagy and may therefore influence mitotic cell cycle progression (Sarraf et al, 2019). PINK1 also regulates both retrograde and anterograde axonal transport of mitochondria via axonal microtubules (Liu et al, 2012) The interaction between PINK1 and parkin is likely involved in mitochondrial quality control mechanisms, where anterograde transport of damaged mitochondria is reduced and retrograde transport is enhanced for elimination by mitophagy in the neuronal cell body (Lionaki et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease

Keo

Dzyubachyk

Hilten

et al. 2020

Preprint

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Cortical atrophy is a common manifestation in Parkinson's disease, particularly in later disease stages. Here, we investigated patterns of cortical thickness using T1-weighted anatomical MRI data of 149 Parkinson's disease patients and 369 controls. To elucidate the molecular underpinnings of cortical thickness changes in Parkinson's disease, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and neuroimaging features. For this purpose, we used partial least squares regression to identify gene expression patterns correlated with cortical thickness changes. In addition, we identified gene expression patterns underlying the relationship between cortical thickness and clinical domains of Parkinson's disease. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in Parkinson's disease are enriched in biological pathways related to sumoylation, regulation of mitotic cell cycle, mitochondrial translation, DNA damage responses, and ER-Golgi traffic. The associated pathways were highly related to each other and all belong to cellular maintenance mechanisms. The expression of genes within most pathways was negatively correlated with cortical thickness changes, showing higher expression in regions associated with decreased cortical thickness (atrophy). On the other hand, sumoylation pathways were positively correlated with cortical thickness changes, showing higher expression in regions with increased cortical thickness (hypertrophy). Our findings suggest that alterations in the balanced interplay of these mechanisms play a role in changes of cortical thickness in Parkinson's disease and possibly influence motor and cognitive functions. Abbreviations: AHBA = Allen Human Brain Atlas; CT = cortical thickness; LED = levodopa equivalent dose; MDS-UPDRS = Movement Disorder Society-sponsored revision of the unified Parkinson's disease rating scale; MMSE = mini-mental state examination; PLS = partial least squares; SENS-PD = severity of non-dopaminergic symptoms in Parkinson's disease Running title: Gene expression and cortical thickness

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“…RNA-seq analysis revealed no difference in the pattern of gene expression between WT and AMPK-KO Th cells recovered at the end of a 14-day culture with DCs and IL-7 (Supplemental Turnover of damaged mitochondria is part of the mitochondrial quality control process and it has recently been shown that enhanced mitophagy can slow-down the cell cycle progression (21). To measure mitochondria turnover in IL-7-treated WT and AMPK-KO Th cell cultures, we pulsed-chased mitochondria with the Mito-Green Tracker probe and followed the Mito-Green loss over time.…”

Section: Ampk Regulates Mitochondrial Fitness In T Cellsmentioning

confidence: 99%

Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of oxygen reactive species

Lepez

Pirnay

Denanglaire

et al. 2020

Preprint

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Under lymphopenia, fast proliferation of peripheral lymphocytes, driven by the availability of interleukin-7 and the engagement of the T cell receptor, results in a large pool of effector/memory T cells that may potentiate anti-tumor immunotherapies but also lead to auto-immune complications.Naïve, effector and memory CD4 T lymphocytes display particular energy metabolism and it has been shown that fine-tuning of cell metabolism might govern T cell differentiation.However, whether T cell metabolism controls homeostatic proliferation is unknown. Here, we report that deficiency in the energy sensor metabolic enzyme AMP-activated kinase (AMPK) results in reduced accumulation of effector/memory T cells during the course of homeostatic proliferation. Accordingly, hematopoietic stem cell transplantation of AMPK-deficient T cells into allogeneic recipient led to a reduced graft-versus-host disease. Moreover, we show that AMPK expression enhances the mitochondrial potential of T cells, limits reactive oxygen species (ROS) production, and resolves ROS-mediated toxicity. Dampening ROS production alleviates the proliferative defect of AMPK-deficient T cells, therefore indicating a role for an AMPK-mediated ROS control of homeostatic proliferation.

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PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis

Cited by 74 publications

References 58 publications

Prognostic significance of autophagy-related genes within esophageal carcinoma

Prognostic significance of autophagy-related genes within esophageal carcinoma

Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease

Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of oxygen reactive species

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