Age-associated dysregulation of post-synaptic mitochondria perturbs re-innervation kinetics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1261070 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33510833_1.fastq.gz | Fastqsanger.gz | |||
| SRR33510833_2.fastq.gz | Fastqsanger.gz | |||
| SRR33510835_1.fastq.gz | Fastqsanger.gz | |||
| SRR33510835_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 29 |
Similar Datasets
Project description:Age-associated degeneration of neuromuscular junctions (NMJs) contributes to sarcopenia and motor decline, yet the mechanisms linking mitochondrial dysfunction to impaired NMJ regeneration in aging remain poorly defined. Here, we demonstrate that post-synaptic mitochondria are significantly diminished in both quantity and bioenergetic function in aged skeletal muscle, correlating with increased denervation and delayed reinnervation following nerve injury. Single-nucleus RNA sequencing of myofibers before and after sciatic nerve crush revealed that sub-synaptic myonuclei in aged muscle exhibit attenuated induction of mitochondrial gene programs, including oxidative phosphorylation, biogenesis, and import. To test whether these deficits are causal, we developed a muscle-specific CRISPR genome editing approach targeting CHCHD2 and CHCHD10—two nuclear-encoded mitochondrial proteins that localize to the intermembrane space and interact with the mitochondrial contact site and cristae organizing system (MICOS). Knockout of CHCHD2/CHCHD10 in young muscle recapitulated aged phenotypes, including mitochondrial disorganization, reduced ATP production, NMJ fragmentation, and delayed reinnervation. Transcriptional profiling of NMJ nuclei from knockout muscles revealed impaired pseudotime progression, failure to activate mitochondrial remodeling programs, and elevated stress signatures. These findings establish a critical role for sub-synaptic mitochondrial integrity in sustaining NMJ stability and regenerative capacity and identify CHCH domain-containing proteins as key regulators of post-synaptic mitochondrial function during aging and injury.
2025-05-16 | GSE296807 | GEO
Project description:Synapses are pivotal sites of plasticity and memory formation. Consequently, synapses are energy consumption hotspots susceptible to dysfunction when their energy supplies are perturbed. Mitochondria are stabilized near synapses via the cytoskeleton and provide the local energy required for synaptic plasticity. However, the mechanisms that tether and stabilize mitochondria to support synaptic plasticity are unknown. We identified proteins exclusively tethering mitochondria to actin near postsynaptic spines. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in amyotrophic lateral sclerosis, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we used two-photon glutamate uncaging for spine plasticity induction and investigated the induced and adjacent uninduced spines. We find VAP functions as a spatial stabilizer of mitochondrial compartments for up to ~60 min and as a spatial ruler determining the ~30 m dendritic segment supported during synaptic plasticity.
2023-11-27 | PXD047226 | Pride
Project description:This study investigates the proteomic alterations in striatal synaptic mitochondria isolated from 3-month-old wild-type and Pink1 KO rats using the SWATH-MS strategy. This dataset consists of 32 raw MS files, comprising 8 DIA (SWATH) and 24 DDA runs on a TripleTOF 5600 (SCIEX). Our findings revealed synaptic mitochondrial proteomic changes due to loss of Pink1.
2016-09-28 | PXD004558 | Pride
Project description:To investigate the role of somatosensory innervation of adipose tissues, we unilaterally ablate sensory innervation of adipose tissues, and profiled the gene expression in the inguinal adipose tissues 4 weeks after sensory ablation surgery.
2022-07-10 | GSE207664 | GEO
Project description:The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication is unknown. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGF1 in parenchymal cells via the IL-17 receptor complex (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGF1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGF1 expression. Ablating cells and the IL-17RC signalling pathway also impairs sympathetic innervation in salivary glands and the lungs. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.
2020-03-02 | PXD017424 | Pride
Project description:The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation. The molecular basis of this bi-directional communication remains to be fully elucidated. We use thermogenic adipose tissue as a model system to show that T cells, specifically gdT cells, play a critical role in promoting sympathetic innervation, at least in part through driving TGFβ1 expression in parenchymal cells via IL-17 Receptor C. Adipose-specific ablation of IL-17 Receptor C reduces TGFβ1 expression in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes consistent with defective thermogenesis; innervation can be fully rescued by restoring TGFβ1 expression. Ablating gdT cells and the IL-17 Receptor C signaling pathway also impairs sympathetic innervation in salivary glands and the lung. These findings demonstrate T cell/parenchymal cell coordination to regulate sympathetic innervation.
2020-02-28 | GSE144255 | GEO
Project description:In this study we hypothesize that early life stress perturbs the normal function of microglial in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 28-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)
2016-05-03 | GSE81037 | GEO
Project description:In this study we hypothesize that early life stress perturbs the normal function of microglia in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 14-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)
2016-05-03 | GSE81036 | GEO
Project description:Osteopontin depletion in macrophages perturbs proteostasis via regulation of UCHL1-UPS pathway and activation of mitochondria-mediated apoptosis
Osteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow derived macrophages (BMM), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMM upregulates OPN expression, promoting an anti inflammatory, phagocytic, pro-healing phenotype, whereas OPN inhibition triggered a pro-inflammatory phenotype. Here, we applied a global proteome profiling via mass spectrometry analysis to gain a mechanistic understanding of OPN suppression versus induction in macrophages. We identified over 630 differentially expressed proteins (DEPs) in OPN knockout (OPNKO) or GA stimulated versus wild type (WT) macrophages. Two topmost downregulated DEPs in OPN deficient macrophages were ubiquitin C terminal hydrolase L1 (UCHL1), a crucial component of ubiquitin proteasome system (UPS), and the anti inflammatory Heme oxygenase 1 (HMOX 1), whereas GA stimulation upregulated their expression. We further confirmed UCHL1 expression in BMM, and its direct interaction with OPN in protein complex. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome mitochondria-mediated apoptosis (e.g. ROS, Lamp1/2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g. 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome bioinformatics data, Western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages, inducing apoptosis and inhibiting translation, whereas GA stimulated OPN induction restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via regulation of cell viability, UCHL1 UPS pathway, and protein synthesis, indicating its potential application in immune-based therapy.
2023-02-08 | MSV000091221 | MassIVE
Project description:camelus dromedarius mitochondria
| PRJEB63970 | ENA