Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SUMOylation of HSPA9 impairs therapeutic efficacy by promoting damaged mitochondria transfer in intervertebral disc degeneration

ABSTRACT: Mitochondrial transfer serves as a crucial mechanism for intercellular communication. The transfer of dysfunctional mitochondria often exacerbates recipient cell impairment, though the underlying mechanisms remain unclear. Here, we demonstrate that senescent stem cells promote inflammation in nucleus pulposus cells by transferring damaged mitochondria via activation of the cGAS-STING-NLRP3 signaling pathway, thereby aggravating intervertebral disc degeneration. Specifically, SUMO3 modification at position 612 of HSPA9 suppresses its ubiquitination-mediated degradation and enhances its binding to damaged mitochondria. Furthermore, we reveal that HSPA9-mediated transfer of dysfunctional mitochondria cooperates with mitophagy to maintain mitochondrial homeostasis in stem cells. Knockdown of HSPA9 and enhancement of mitophagy in senescent stem cells resulted in microvesicles that were independent of the parental cell’s functional state, ultimately promoting therapeutic outcomes against intervertebral disc degeneration.

ORGANISM(S): Homo Sapiens

SUBMITTER: Cao Yang

PROVIDER: PXD072918 | iProX | Sat Jan 10 00:00:00 GMT 2026

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin; germline Parkin knockout mouse hearts.

Project description:Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. 5 wild-type mouse hearts; 4 germline Parkin knockout mouse hearts Please note that the mouse cardiac examples were an adjunct to the Drosophila studies that comprised most of the associated publication. However, mRNA-sequencing was only performed on the mouse samples, not the Drosophila heart tubes.

2015-10-31 | E-GEOD-74517 | biostudies-arrayexpress

Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin; germline Parkin knockout mouse hearts.

2015-10-31 | GSE74517 | GEO

Intervertebral disc degeneration

Project description:Intervertebral disc degeneration

| PRJNA962588 | ENA

cGAS-STING axis activation drove inflammatory phenotype acquisition of senescent nucleus pulposus cells via p65-mediated transcriptional modulation

Project description:Given the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socio-economic challenge to the aging population, which is importantly attributed to intervertebral disc degeneration (IVDD), a highly prevalent affliction of aging. Elastic nucleus pulposus (NP) tissue is essential for maintenance of IVD structural and functional integrity. Native NP cells exhibit crucial functions for regulating extracellular matrix homeostasis, constructing an accommodating biomechanical environment and maintaining the gelatinous property of NP tissue. The accumulation of senescent NP cells with inflammatory hypersecretory phenotype due to aging and other damaged factors is a distinctive hallmark of IVDD initiation and progression. In this study, we revealed a mechanism of IVDD progression in which aberrant genomic DNA damage promotes NP cell inflammatory senescence via activation of cGAS-STING axis. cGAS-STING axis activation drove inflammatory phenotype acquisition and inflammatory hypersensitivity to damaged signals of senescent NP cells via p65-mediated transcriptional modulation. And STING pharmacological inhibitor notably suppressed p65-mediated inflammatory response formation and senescence-associated screctory phenotype (SASP) acquisition of senescent cells.

2024-03-20 | GSE244403 | GEO

Transcriptome analysis of CHSY3 knockdown NP cells

Project description:Intervertebral disc degeneration is the main cause of low back pain and the mechanism of which is far from fully revealed. Although multiple factors are related to the intervertebral disc degeneration, inflammation and matrix metabolism dysregulation are the two key factors that play an important role in degeneration. Here, we found that CHSY3 is highly related to the nucleus pulposus degeneration. We generated CHSY3 knockout mice using Crisper/Cas9 system, and the NP cells are studied in this experiment.

2022-01-02 | GSE145649 | GEO

Tagln+ progenitors contribute to the development and maintenance of nucleus pulposus

Project description:Failure of intervertebral disc components, e.g. the nucleus pulposus causes intervertebral disc disease and associated low-back pain. Despite the high prevalence of disc disease, the changes in intervertebral disc cells and their regenerative potential with ageing and degeneration are not fully elucidated. Understanding the cell lineage, cell differentiation and maintenance of nucleus pulposus may have therapeutic application for the regeneration of degenerative disc, with significant impact for healthy ageing. Here we found that TAGLN expressing cells are present in human healthy nucleus pulposus, but diminish in degenerative disc. By lineage analyses in mice, we found cells in the nucleus pulposus are derived from a peripherally located population of notochord-derived Tagln expressing cells (PeriNP cells). The PeriNP cells are proliferative and can differentiate into the inner part of the nucleus pulposus. The Tagln+ cells and descendants diminish during aging and puncture induced disc degeneration. The maintenance and differentiation of PeriNP cells is partially regulated by Smad4 dependent signaling. Removal of Smad4 by nucleus pulposus specific Cre (Foxa2mNE-Cre), results in decreased Tagln+ cells and abnormal disc morphology, leading to disc degeneration. Our findings propose that the PeriNP Tagln expressing cells are a pool of notochord-derived progenitors that are important for maintenance of the nucleus pulposus and provide insights for regenerative therapy against intervertebral disc degeneration.

2024-05-14 | GSE186549 | GEO

Opposing roles for AMPK in regulating distinct mitophagy pathways

Project description:Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. While AMPK, the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear. We found that AMPK directly inhibits NIX-dependent mitophagy by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 and an additional identified site, Ser694. In contrast, AMPK activation increases Parkin phosphorylation and enhances the rate of depolarisation-induced mitophagy, independently of ULK1. We show that this happens both in cultured cells and tissues in vivo, using the mito-QC mouse model. Our work unveils a mechanism whereby AMPK activation downregulates mitophagy of functional mitochondria but enhances that of dysfunctional/damaged ones.

2024-11-29 | PXD056956 | Pride

Multi-omics Analysis and Evidence of IL1R1 as a Potential Biomarker for Diabetes-related Intervertebral Disc Degeneration

Project description:This study employs 10x Genomics single-cell RNA sequencing (scRNA-seq) to profile cellular changes within the intervertebral discs of diabetic mice. Diabetes mellitus is a systemic inflammatory disease known to drive pathological alterations in multiple organ systems. Here, we specifically investigate the process of diabetes-induced intervertebral disc degeneration. Our findings aim to provide novel insights into the pathogenic mechanisms underlying disc degeneration.

2025-10-27 | GSE305927 | GEO

Proteomics for patients with intervertebral disc degeneration

Project description:Proteomics for patients with intervertebral disc degeneration

2024-04-10 | PXD051351 |

Mitochondrial Transfer Regulates Cell Fate Through Metabolic Remodeling in Osteoporosis

Project description:Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, we examined mesenchymal stem cell (MSC) regulation by macrophages in the bone marrow environment. We found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes and metabolic statuses release oxidatively damaged mitochondria. The transfer of dysfunctional mitochondria to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. We showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.

2022-09-11 | GSE198806 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data