Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis are prominent features of aprataxin-deficient cells

ABSTRACT: Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis are prominent features of aprataxin-deficient cells

PROVIDER: PRJNA472617 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells

Project description:Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells

| PRJNA511981 | ENA

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis are prominent features of aprataxin-deficient cells

Project description:Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset progressive spinocerebellar ataxia caused by mutation in aprataxin (APTX). APTX removes 5´-AMP groups from DNA, a product of abortive ligation during DNA repair and replication. APTX deficiency has been suggested to compromise mitochondrial function; however, a detailed characterization of mitochondrial homeostasis in APTX-deficient cells is not available. Here we show that cells lacking APTX undergo mitochondrial stress and display significant changes in the expression of the mitochondrial inner membrane fusion protein OPA1, and components of the oxidative phosphorylation complexes. At the cellular level, APTX deficiency impairs mitochondrial morphology and network formation, and autophagic removal of damaged mitochondria by mitophagy. Thus, our results show that aberrant mitochondrial function is a key component of AOA1 pathology. This work corroborates the emerging evidence that impaired mitochondrial dynamics and mitophagy are at the hub of an increasing number of genetically diverse neurodegenerative disorders.

2019-05-21 | GSE114786 | GEO

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis are prominent features of Aprataxin-deficient cells

Project description:Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset progressive spinocerebellar ataxia caused by mutation in aprataxin (APTX). Here we use RNA-seq to identify genes that are affected by APTX-KO, APTX overexpression, and APTX mutant, thus contributes to understadning the mechanisms underlying AOA1 pathlogy. Examination the chages of gene expressions in APTX proficient and APTX deficienc cells.

2018-12-28 | E-GEOD-124412 | biostudies-arrayexpress

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells

Project description:Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset progressive spinocerebellar ataxia caused by mutation in aprataxin (APTX). Here we use RNA-seq to identify genes that are affected by APTX-KO, APTX overexpression, and APTX mutant, thus contributes to understadning the mechanisms underlying AOA1 pathlogy. Published: https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz083/5319145

2018-12-28 | GSE124412 | GEO

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells.

Project description:Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset progressive spinocerebellar ataxia caused by mutation in aprataxin (APTX). APTX removes 5'-AMP groups from DNA, a product of abortive ligation during DNA repair and replication. APTX deficiency has been suggested to compromise mitochondrial function; however, a detailed characterization of mitochondrial homeostasis in APTX-deficient cells is not available. Here, we show that cells lacking APTX undergo mitochondrial stress and display significant changes in the expression of the mitochondrial inner membrane fusion protein optic atrophy type 1, and components of the oxidative phosphorylation complexes. At the cellular level, APTX deficiency impairs mitochondrial morphology and network formation, and autophagic removal of damaged mitochondria by mitophagy. Thus, our results show that aberrant mitochondrial function is a key component of AOA1 pathology. This work corroborates the emerging evidence that impaired mitochondrial function is a characteristic of an increasing number of genetically diverse neurodegenerative disorders.

| S-EPMC6486572 | biostudies-literature

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells

Project description:Regulation of quiescence is essential for adult stem cell maintenance, longevity and sustained regeneration potential. Our studies have uncovered that physiological and transient changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that mitochondria in MuSCs rapidly fragment in response to an activation stimulus, via a systemic HGF/mTOR mechanism, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and forced mitochondrial fragmentation is sufficient to transition MuSCs into G-alert quiescence causing premature activation and depletion upon a stimulus. Loss of OPA1 activates a glutathione (GSH) redox signaling pathway that promotes cell-cycle progression, myogenic gene expression and commitment. MuSCs with chronic OPA1 loss and mitochondrial fragmentation, leading to mitochondrial dysfunction, continue to reside in a primed state but acquire severe cell cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics may contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.

2022-08-24 | GSE208326 | GEO

Necroptosis inhibition protects from dopaminergic neuronal cell death in OPA1 mutant Parkinson’s disease patient neurons and MPTP treated mice

Project description:Dysfunctions in mitochondria dynamics and metabolism are common pathological processes associated with Parkinson’s disease (PD). Recently, it was shown that an inherited form of PD and dementia is caused by new mutations in the OPA1 gene, which encodes for a key player of mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1 mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectively rescued this survival deficit. Additionally, dampening necroptosis in MPTP treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both the early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a promising therapeutic target for PD.

2019-01-16 | GSE109228 | GEO

Heart proteome in Cox10 depending on Opa1 processing

Project description:Mitochondrial fusion and fission accompany adaptive responses to stress and altered metabolic demands. Inner membrane fusion and cristae morphogenesis depends on Optic Atrophy 1 (Opa1), which is expressed in different isoforms and is cleaved from a membrane-bound, long to a soluble, short form. Here, we have analyzed the physiological role of Opa1 isoforms and Opa1 processing by generating mouse lines expressing only one cleavable Opa1 isoform or a non-cleavable variant thereof. Our results show that expression of a single cleavable or non-cleavable Opa1 isoform preserves embryonic development and the health of adult mice. Opa1 processing is dispensable under metabolic and thermal stress, but prolongs lifespan and protects against mitochondrial cardiomyopathy in OXPHOS-deficient Cox10-/- mice. Mechanistically, loss of Opa1 processing disturbs the balance between mitochondrial biogenesis and mitophagy, suppressing cardiac hypertrophic growth in Cox10-/- hearts. Our results highlight the critical regulatory role of Opa1 processing, mitochondrial dynamics and metabolism for cardiac hypertrophy.

2024-08-10 | PXD048804 | Pride

Genome-wide analysis of Ctr and OPA1 knock-down transcriptomes

Project description:Through the genome-wide analysis of Ctr and OPA1 knock-down group, we reveal the transcriptome changes with OPA1 down-regulation

2019-07-31 | GSE135089 | GEO

OPA1 mice gut micobiome

Project description:OPA1 mice gut micobiome

| PRJEB83275 | ENA