PTEN-induced kinase 1 (PINK1) ameliorates autoimmune disease via negative regulation of the STAT3-Th17 axis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE254099 | GEO | 2024/01/29
REPOSITORIES: GEO
Similar Datasets
Project description:The maintenance of mitochondrial homeostasis requires PTEN-induced kinase 1 (PINK1)-dependent mitophagy, and mutations in PINK1 are associated with Parkinson's disease (PD). PINK1 is also downregulated in tumor cells with PTEN mutations. However, there is limited information concerning the role of PINK1 in tissue growth and tumorigenesis. Here, we show that loss of pink1 caused multiple growth defects independent of its pathological target, Parkin. Moreover, knocking-down pink1 in muscle cells induced hyperglycemia and limited systemic organismal growth by induction of Imaginal morphogenesis protein-Late 2 (ImpL2). Similarly, disrupting PTEN activity in multiple tissues impaired systemic growth by reducing pink1 expression, resembling wasting-like syndrome in cancer patients. Furthermore, re-expression of PINK1 fully rescued defects in carbohydrate metabolism and systemic growth induced by the tissue-specific pten mutations. Our data suggest a new function for PINK1 in regulating systemic growth in Drosophila, and shed light on its role in wasting in context of PTEN mutations.
2021-02-20 | GSE167076 | GEO
Project description:Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD. Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of M-NM-1-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. Thus, aging Pink1M-bM-^HM-^R/M-bM-^HM-^R mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Transcriptome microarray data of Pink1-/- mouse brains in absence of a stressor, even at old age, show remarkably sparse dysregulations. See Gispert-S et al 2009 PLOS ONE. Factorial design comparing Pink1 knock-out mice with wild type littermates in three different tissues (striatum, midbrain, cerebellum at four different timepoints (6, 12, 14 weeks, and 18 month)
2014-11-04 | E-GEOD-60413 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD. Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of α-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. Thus, aging Pink1−/− mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Transcriptome microarray data of Pink1-/- mouse brains in absence of a stressor, even at old age, show remarkably sparse dysregulations. See Gispert-S et al 2009 PLOS ONE.
2014-11-04 | GSE60413 | GEO
Project description:Age-related macular degeneration (AMD), the leading cause of blindness among the elderly, is without effective treatment for early, dry disease. Retinal pigment epithelial (RPE) cell degeneration is a cardinal feature of dry AMD. Given the reliance of photoreceptors on the RPE for maintaining health and vision, rejuvenating dysfunctional RPE is a logical treatment strategy. Here, the interplay between two cytoprotective pathways, Pink1 mediated mitophagy and the Nrf2 stress-response, was studied in human AMD tissue samples, RPE cells, and relevant mouse models. Pink1 immunolabeling was decreased in the RPE of early AMD eyes. The RPE from Pink1-/- mice and Pink1 deficient cultured human RPE cells displayed impaired mitophagy, decreased aerobic respiration, and increased mitochondrial reactive oxygen species (ROS) generation, and coincidently, developed morphological, molecular, and functional features of epithelial-mesenchymal transition (EMT). This change was triggered by novel retrograde mitochondrial to nuclear signaling that was initiated by mitochondrial ROS, which activated Nrf2 to induce TXNRD1, PI3K/AKT, and canonical EMT transcription factors Zeb1 and Snail. Nrf2 signaling was pivotal since its deficiency prevented EMT and increased cell death. A dendrimer containing N-acetyl cysteine that is tropic for the RPE and contains the mitochondrial targeting ligand Triphenyl phosphinium abrogates EMT in human RPE cells in vitro and in Pink1-/- mice. This study describes a novel interdependency of mitophagy and the Nrf2 antioxidant response in determining cell fate and introduces an RPE and mitochondrial specific ROS reducing dendrimer that can rescue RPE cells in EMT, a change recognized in early AMD.
2022-01-01 | GSE186751 | GEO
Project description:Global analysis of transcriptional changes in Drosophila pink1 mutants.
2013-12-02 | E-MEXP-3645 | biostudies-arrayexpress
Project description:A549 cells were transduced with a lentivirus expressing lnc-PINK1-2:5 at a MOI of 200 for 48 h. The cells were then infected with PR/8 at a MOI of 0.01 for 48 h. RNA-seq was done on the RNA samples from three vector control and three lnc-PINK1-2:5-overexpressing cells.
2021-07-13 | GSE179747 | GEO
Project description:PTEN-induced kinase 1 (PINK1) is a very short-lived protein that is required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated with and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane protein Synaptojanin 2 Binding Protein (SYNJ2BP) and Synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for activation of mitophagy.
2022-01-14 | GSE193443 | GEO
Project description:Loss of function in the PTEN-induced kinase 1 gene (Pink1) causes an early-onset, autosomal recessive form of PD. The translational Pink1-/- rat shows cranial sensorimotor deficits including: declines in ultrasonic vocalization, negative impacts on social vocal function, and alterations to thyroarytenoid muscle structure. The aim of this study was to identify differentially expressed genes using RNA-sequencing and bioinformatic analysis of the thyroarytenoid muscle of male Pink1-/- rats compared to wildtype controls. To construct gene co-expression networks and gene modules, a WGCNA was used to identify biological networks of interest including where Pink1 was a central node with interconnecting genes. Data are congruent with previous findings demonstrating changes to thyroarytenoid muscle structure. These data are consistent with the hypothesis that differences in peripheral biology may influence the early pathogenesis of vocalizations at the level of the thyroarytenoid muscle.
2020-05-27 | GSE151209 | GEO
Project description:To investigate the PINK1 regulates mitochondrial function, we performed the gene expression data for two independent libraries for Pink1-/- and Pink1+/+ mice, at two different time points, 4 and 24 months.
2023-05-16 | GSE217775 | GEO
Project description:Analysis of mRNA expression in the brains (cortex) of 6 months-old PINK1 knockout mice.
2014-07-20 | E-MTAB-2461 | biostudies-arrayexpress