Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative Proteomic Profiling of Tau-Knockout and Wild-Type Mouse Hippocampus

ABSTRACT: Mitochondria fuse, divide, and interact with other organelles to adjust cellular fitness while they provide energy to sustain neuronal activity and health. In contrast to plethora of evidence reporting that accumulation of pathological Tau damages mitochondria function promoting neurodegeneration, there is limited knowledge about the physiological role of Tau on the maintenance of mitochondrial homeostasis. Our mice and C. elegans studies provide multiscale evidence that loss of Tau or its nematode homolog, PTL-1, enhances mitochondrial function and mitochondria quality control promoting a profusion state via mitofusins, that leads to reduced vulnerability to mitochondria stress. Overall, our findings provide solid evidence about the fine-tuning role of Tau protein on mitochondrial function and dynamics in neurons based on two different organisms.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hippocampus

SUBMITTER: Martina Samiotaki

LAB HEAD: Ioannis Sotiropoulos

PROVIDER: PXD073466 | Pride | 2026-06-15

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20196_1.raw	Raw
	20196_2.raw	Raw
	20197_1.raw	Raw
	20197_2.raw	Raw
	20198_1.raw	Raw

Items per page:

1 - 5 of 21

Similar Datasets

Differential Proteomics of Ptl-1 KO and Control C.elegans

Project description:Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations are known to impair mitochondrial dynamics and function, the physiological role of wild-type Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using C. elegans and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency enhances mitochondrial respiration, ATP production and mitophagy, promoting a pro-fusion mitochondrial network in neurons. Tau-deficient nematodes also display increased resistance to stressors, including heat and mitochondrial insults. Strikingly, loss of FZO-1, the mitofusin homolog, abolishes these effects, reducing mitochondrial function and stress resistance in PTL-1 deficient nematodes. Our findings reveal a conserved role for wild-type Tau in restraining mitochondrial fusion and activity via mitofusins, highlighting its contribution to mitochondrial quality control and cellular stress resilience.

2026-06-15 | PXD073360 | Pride

Modulating mitofusins to control mitochondrial function and signaling

Project description:Purpose: Mitofusin regulate the fusion of the outer mitochondrial membrane. MASM7 is an activator of mitofusins, which promotes mitochondrial fusion. Whereas, MFI8 is an inhibitor of mitofusins, which inhibits mitochondrial fusion, and subsequently promotes mitochondrial fission. The goal of this study is to identify set of genes and pathways that are up-regulated upon inhibition and activation of mitochondrial fusion.

2022-06-21 | GSE186924 | GEO

Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.

Project description:Paracetamol (acetaminophen, APAP) overdose severely damages mitochondria and triggers several apoptotic processes in hepatocytes, but the final outcome is fulminant necrotic cell death, resulting in acute liver failure and mortality. Here, we studied this switch of cell death modes and demonstrate a non-canonical role of the apoptosis-regulating BCL-2 homolog BIM/Bcl2l11 in promoting necrosis by regulating cellular bioenergetics. BIM deficiency enhanced total ATP production and shifted the bioenergetic profile towards glycolysis, resulting in persistent protection from APAP-induced liver injury. Modulation of glucose levels and deletion of mitofusins confirmed that severe APAP toxicity occurs only in cells dependent on oxidative phosphorylation. Glycolytic hepatocytes maintained elevated ATP levels and reduced ROS, which enabled lysosomal recycling of damaged mitochondria by mitophagy. The present study highlights how metabolism and bioenergetics affect drug-induced liver toxicity, and identifies BIM as important regulator of glycolysis, mitochondrial respiration, and oxidative stress signaling.

2023-09-08 | GSE242368 | GEO

Mitophagy ameliorates Aβ and p-Tau pathologies, and cognitive deficits, in experimental models of Alzheimer’s disease

Project description:Accumulation of damaged mitochondria is a hallmark of human aging and age-related neurodegenerative pathologies, including Alzheimer’s disease (AD). However, the molecular mechanisms of the impaired mitochondrial homeostasis and their relationship to AD are still elusive. Here we provide evidence that mitophagy, a cellular process mediating selective clearance of dysfunctional mitochondria, is impaired in AD patient hippocampus, in iPSC-derived human neurons and in animal AD models. In C. elegans models of AD, pharmacological stimulation of mitophagy reverses memory impairment through a PINK-1, PDR-1 and DCT-1 dependent pathway. Mitophagy induction diminishes the levels of insoluble amyloid-β (Aβ)1-42 and Aβ1-40 peptide isoforms and prevents cognitive impairment in AD mice by a mechanism involving microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Furthermore, mitophagy abolishes AD-related Tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic Tau nematodes. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis. Interventions that stimulate mitophagy therefore have therapeutic potential in the prevention and treatment of AD.

2018-11-26 | GSE111737 | GEO

MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation.

Project description:MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by Ago2 CrossLinking ImmunoPrecipitation coupled with sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm. Examination of miRNA's regulation function in mitochondria in C2C12 myoblasts cells and myotubes cells with CLIP-seq (Ago2).

2014-08-01 | E-GEOD-57596 | biostudies-arrayexpress

Locus coeruleus vulnerability to tau hyperphosphorylation in a rat model

Project description:Post-mortem investigations indicate that the locus coeruleus (LC) is the initial site of hyperphosphorylated pretangle tau, a precursor to neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD). The presence of pretangle tau and NFTs in the LC correlates with AD progression. LC neuron integrity and quantity are linked to cognitive states, with degeneration associated with AD. However, the mechanisms of pretangle tau-induced LC degeneration are unclear. This study examined the transcriptomic and mitochondrial profiles of LC noradrenergic neurons after transduction with pseudophosphorylated human tau. Tau hyperphosphorylation increased the somatic expression of the L-type calcium channel (LTCC), impaired mitochondria health, and led to deficits in spatial and olfactory learning. Sex-dependent alterations in gene expression were observed in rats transduced with pretangle tau. Chronic LTCC blockade prevented behavioral deficits and altered mitochondrial mRNA expression, suggesting a potential link between LTCC hyperactivity and mitochondrial dysfunction. Our research provides insights into the consequences of tau pathology in the originating structure of AD.

2024-11-16 | GSE272794 | GEO

Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis

2024-09-24 | PXD045034 | Pride

Mesenchymal Stem Cells Transfer Mitochondria to the Cells with Virtually Absent Mitochondrial Function but Not to the Cells Harboring Pathogenic Mitochondrial DNA Mutations

Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B 0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction. time series

2011-11-22 | E-GEOD-33831 | biostudies-arrayexpress

mitoCPR - a surveillance pathway that protects mitochondria in response to mitochondrial import stress [yeast]

Project description:Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Physiological perturbations and disease conditions can lead to mitochondrial import defect. We find that in budding yeast, mitochondrial import defects result in activation of a surveillance mechanism, which we termed mitoCPR. The mitoCPR is aimed at ameliorating mitochondrial import and protecting mitochondria during import stress. This is mediated by the mitoCPR effector, Cis1, which associates with mitochondria to reduce the accumulation of mitochondrial preproteins at the organelle's surface. Clearance of preproteins depends on the AAA-ATPase Msp1 and the proteasome, suggesting that Cis1 facilitates the degradation of unimported proteins that accumulate at the mitochondrial surface. We further show that mitoCPR is critical for maintaining mitochondrial functions during mitochondrial import stress and provide evidence that it is an ancient, conserved mitochondrial protection mechanism.

2019-03-16 | GSE96727 | GEO

mitoCPR - a surveillance pathway that protects mitochondria in response to mitochondrial import stress [human]

2019-03-16 | GSE96726 | GEO