Loss of pex5 sensitizes zebrafish to fasting due to deregulated mitochondria, mTOR, and autophagy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA844556 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19520282_1.fastq.gz | Fastqsanger.gz | |||
| SRR19520282_2.fastq.gz | Fastqsanger.gz | |||
| SRR19520283_1.fastq.gz | Fastqsanger.gz | |||
| SRR19520283_2.fastq.gz | Fastqsanger.gz | |||
| SRR19520284_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSD), but the link between the clinical manifestations and molecular pathways has not yet been clearly established. We generated a peroxin 5 homozygous mutant zebrafish (pex5-/-) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5-/- displays hallmarks of ZSD in humans and die within one month after birth. Fasting rapidly depletes the liver lipids and glycogen in pex5-/- and expedites their mortality. Mechanistically, abnormal mitochondrial activity and mechanistic target of rapamycin (mTOR) signaling act together to induce metabolic alterations to deplete the hepatic nutrients and accumulate the damaged mitochondria. Accordingly, the use of chemical interventions blocking either the mitochondrial activities or the mechanistic target of rapamycin complex 1 or a combination of both improves the metabolic imbalance shown in the fasted pex5-/- livers and extends the survival of the animals. Furthermore, the use of an autophagy activator also effectively ameliorated the early mortality of the fasted pex5-/-. These results suggest that fasting may be detrimental to patients with peroxisome dysfunction and that modulating the mitochondria, mTOR, or autophagy activities may provide a therapeutic option to alleviate the symptoms of peroxisomal diseases associated with metabolic dysfunction.
2022-06-05 | GSE205349 | GEO
Project description:Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSDs); however, the link between clinical manifestations and molecular pathways has not yet been clearly established. We generated peroxin 5 homozygous mutant zebrafish (pex5-/-) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5-/- display hallmarks of ZSD in humans and die within one month after birth. Fasting rapidly depletes lipids and glycogen in pex5-/- livers and expedites their mortality. Mechanistically, deregulated mitochondria and mechanistic target of rapamycin (mTOR) signaling act together to induce metabolic alterations that deplete hepatic nutrients and accumulate damaged mitochondria. Accordingly, chemical interventions blocking either the mitochondrial function or mTOR complex 1 (mTORC1) or a combination of both improve the metabolic imbalance shown in the fasted pex5-/- livers and extend the survival of animals. In addition, the suppression of oxidative stress by N-acetyl L-cysteine (NAC) treatment rescued the apoptotic cell death and early mortality observed in pex5-/-. Furthermore, an autophagy activator effectively ameliorated the early mortality of fasted pex5-/-. These results suggest that fasting may be detrimental to patients with peroxisome dysfunction, and that modulating the mitochondria, mTORC1, autophagy activities, or oxidative stress may provide a therapeutic option to alleviate the symptoms of peroxisomal diseases associated with metabolic dysfunction.
| S-EPMC9950184 | biostudies-literature
Project description:These arrays contain data from gonodal adipose tissue of aP2-Pex5 -/- male mice 4 arrays from gonadal adipose tissue from control mice (Swiss background) are compared with 4 arrays from gonadal adipose tissue of aP2-Pex5 knockout mice. The latter lack functional peroxisomes in adipose tissue.
2012-03-01 | E-GEOD-31940 | biostudies-arrayexpress
Project description:This project sought to identify the features in PEX5 required for interaction with the peroxisomal PEX2-PEX10-PEX12 ubiquitin ligase complex. Peroxisomes equilibrated with different PEX5 mutants (i.e., C11A, AH1, AH2) were purified from Xenopus egg extract, solubilized in digitonin, and PEX5-associated material was immunoprecipitated via a C-terminal FLAG tag. PEX5 without a FLAG tag was used as a negative control. PEX5-interacting peroxins were identified by LC-MS/MS at the Taplin Mass Spectrometry Facility at Harvard Medical School.
2022-08-16 | PXD035105 | Pride
Project description:These arrays contain data from gonodal adipose tissue of aP2-Pex5 -/- male mice
2012-03-01 | GSE31940 | GEO
Project description:Chronic lung diseases significantly impact the aging population globally, but their etiology is largely unknown, and the therapeutic options are minimal. Cellular senescence has been increasingly recognized as an essential driving mechanism for chronic lung diseases. Remodeling in subcellular compartments is commonly observed in senescent cells, which reciprocally regulates the senescent progression. Roles of peroxisomes in cellular senescence have been documented, but the molecular mechanisms for this regulation remain poorly understood. Here, we showed that the peroxisome pathway and the shuttling receptor PEX5 are downregulated during replicative and oxidative senescence in human fetal lung fibroblast 1 (HFL-1) cells. PEX5 knockdown can induce senescence via transcriptional suppression of LAMP1 and autophagic flux. Further study revealed that activation of the p38 MAPK signaling pathway and subsequent nuclear localization of transcription factor EB (TFEB) are the significant retrograde signals contributing to the PEX5 regulation of cellular senescence. Metabolomics analysis identified a substantial increase in taurine levels in cells with PEX5 overexpression. Reciprocally, treatment of cells with taurine enhanced PEX5 levels in the senescent HFL-1 cells and the lungs of aged mice and alleviated senescence, suggesting the presence of a taurine-dependent response in PEX5 regulation of cellular senescence. Collectively, our findings provided new insights into the peroxisomal regulation of cellular senescence by integrating the p38 MAPK retrograde signaling pathway and taurine metabolism, which may help develop anti-aging strategies to treat chronic lung diseases.
2024-04-16 | GSE263751 | GEO
Project description:We generated a muscle-specific Pex5 KO mouse to investigate the consequences of peroxisomal dysfunction on muscle homeostasis. Our study reveals that peroxisomal impairment triggers early alterations in skeletal muscle lipid and amino acid metabolism and disrupts the physical interaction between peroxisomes and mitochondria, resulting in reduction of muscle force and exercise performance. Over time, these disruptions lead to metabolic changes that affect mitochondrial content, and function anticipating the development of age-related muscle dysfunction.
2025-09-16 | GSE263105 | GEO
Project description:We generated a muscle-specific Pex5 KO mouse to investigate the consequences of peroxisomal dysfunction on muscle homeostasis. Our study reveals that peroxisomal impairment triggers early alterations in skeletal muscle lipid and amino acid metabolism and disrupts the physical interaction between peroxisomes and mitochondria, resulting in reduction of muscle force and exercise performance. Over time, these disruptions lead to metabolic changes that affect mitochondrial content, and function anticipating the development of age-related muscle dysfunction.
2025-09-16 | GSE263104 | GEO
Project description:We generated a muscle-specific Pex5 KO mouse to investigate the consequences of peroxisomal dysfunction on muscle homeostasis. Our study reveals that peroxisomal impairment triggers early alterations in skeletal muscle lipid and amino acid metabolism and disrupts the physical interaction between peroxisomes and mitochondria, resulting in reduction of muscle force and exercise performance. Over time, these disruptions lead to metabolic changes that affect mitochondrial content, and function anticipating the development of age-related muscle dysfunction.
2025-09-16 | GSE263103 | GEO
Project description:Lipid droplets (LDs) are key subcellular organelles for regulating lipid metabolism. Although several subcellular organelles participate in lipid metabolism, it remains elusive whether physical contacts between subcellular organelles and LDs might be involved in lipolysis upon nutritional deprivation. Here, we demonstrate that peroxisomes and peroxisomal protein PEX5 mediate fasting-induced lipolysis by stimulating adipose triglyceride lipase (ATGL) translocation onto LDs. During fasting, physical contacts between peroxisomes and LDs are increased by KIFC3-dependent movement of peroxisomes toward LDs, which facilitates spatial translocations of ATGL onto LDs. In addition, PEX5 could escort ATGL to contact points between peroxisomes and LDs in the presence of fasting cues. Moreover, in adipocyte-specific PEX5-knockout mice, the recruitment of ATGL onto LDs was defective and fasting-induced lipolysis is attenuated. Collectively, these data suggest that physical contacts between peroxisomes and LDs are required for spatiotemporal translocation of ATGL, which is escorted by PEX5 upon fasting, to maintain energy homeostasis.
| S-EPMC6989686 | biostudies-literature