Mitochondrial protease Lonp1 localizes to the nucleus in response to heat shock
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164834 | GEO | 2022/06/28
REPOSITORIES: GEO
Similar Datasets
Project description:Mitochondrial protease Lonp1 localizes to the nucleus in response to heat shock
| PRJNA692181 | ENA
Project description:Mitochondria serve diverse functions and are essential organelles that require continuous surveillance to maintaintheir integrity and function. LONP1 is an evolutionarily conservedserine peptidase that safeguards mitochondrial protein quality from yeast to human.To investigatethe physiological role of LONP1-mediated mitochondrial quality-control in skeletal musclein vivo, we generated skeletal muscle-specificLonp1-knockout mice (referred to as LONP1 MKO). We performedtranscriptome analysis by whole-genome gene expression profiling experiments in gastrocnemius (GC) muscle from both wild-type (WT) and LONP1-MKO mice. Knockout of LONP1 in skeletal muscle resulted in deregulation of 457 genes in 2-week-old mice and of 1922 genes in 6-week-old mice. Gene ontology analysis revealed that LONP1 deficiency triggers unfolded protein response (UPR) in skeletal muscle.Moreover, GSEA analysis of transcriptomic datain 6-week-old micefurther revealed that genes deregulated by LONP1 deficiency were significantly enriched during aging.Together, the transcriptional profiling results suggest a critical role of LONP1 in regulating skeletal muscle metabolism and health.
2022-01-05 | GSE166071 | GEO
Project description:Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity acting both as protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. It remains unclear, however, whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switch such as white-to-beige conversion of adipocytes. We found that disruption of LONP1-dependent proteolysis substantially impairs thermogenic molecular program and cellular respiration in in vitro differentiated primary adipocytes. qPCR analysis showed that expression levels of Ucp1 and other beige adipocyte thermogenic genes were remarkably downregulated in LONP1 AKO adipocytes. We took a deeper dive into the characterization of histone modifications in LONP1 AKO adipocytes using the global enhancer marker H3K4me1 ChIP-Seq. These unbiased ChIP seq data are strong evidence of that LONP1 loss results in decreased H3K4me1 on a broad array of thermogenic genes. These results collectively indicate that LONP1 is crucial to maintain proper epigenetic homeostasis and beige thermogenic gene expression.
2023-04-08 | GSE222490 | GEO
Project description:Studying the molecular basis for the skeletal muscle mitochondrial stress response could potentially be targeted to counteract metabolic disorders such as obesity. We uncovered a crucial role for the mitochondrial protease LONP1 in controlling the muscle mitochondrial proteostasis stress response that governs systemic metabolic homeostasis. Skeletal muscle-specific ablation of LONP1 led to broad genomic reprogramming of muscle and protected the mice from HFD-induced obesity. To thoroughly analyze pathways that are affected by ATF4 deficiency in the context of LONP1 mKO, we performed RNA-Seq transcriptome analysis of skeletal muscles from WT, LONP1 mKO and LONP1ATF4 DmKO mice. We identified a total of 3017 differentially expressed genes with a cutoff of 1.5-fold, and p < 0.05. Surprisingly, we found that ATF4 loss blunted a subset of regulated genes in LONP1 mKO muscles, whereas the majority of differentially regulated genes in LONP1 mKO muscles were not affected by ATF4 ablation. GO analysis of ATF4-dependent genes regulated by LONP1 ablation revealed significant enrichment in amino acid metabolic processes, Interestingly, however, LONP1 deficiency induced activation of muscle UPR and UPR-related RNA processing as well as myokine pathways were not affected by ATF4 ablation. Therefore, our results highlight a ATF4-independent mechanism in mediating the UPRmt in mammals.
2022-07-28 | GSE192990 | GEO
Project description:The mitochondrial matrix protease LONP1 is an essential part of the organellar protein quality control system. LONP1 has been shown to be involved in respiration control and apoptosis. Furthermore, a reduction in LONP1 level correlates with ageing processes. Up to now, the effects of a LONP1 defect were mostly studied by utilizing transient, siRNA-mediated knockdown approaches. We generated a new cellular model system for studying the impact of LONP1 on mitochondrial protein homeostasis by a CRISPR/Cas-mediated genetic knockdown (gKD). These cells show a stable reduction of LONP1 along with a mild phenotype characterized by absent morphological differences and only small negative effects on mitochondrial functions under normal culture conditions. To assess the consequences of a permanent LONP1 depletion on the mitochondrial proteome, we analyzed the alterations of protein levels by quantitative mass spectrometry, demonstrating small adaptive changes, in particular concerning mitochondrial protein biogenesis. In an additional proteomic analysis, we determined the temperature-dependent aggregation behavior of mitochondrial proteins and its dependence on a reduction of LONP1 activity, demonstrating the important role of the protease for mitochondrial protein homeostasis in mammalian cells. We identified a significant number of mitochondrial proteins that are affected by LONP1 activity concerning their stressinduced solubility. Taken together, our results suggest a very good applicability of the LONP1 gKD cell line as a model system for human ageing processes.
2022-01-31 | PXD026941 | Pride
Project description:The mitochondrial protease LonP1 promotes proteasome inhibitor resistance in multiple myeloma.
| PRJNA699295 | ENA
Project description:Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response
(HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular
chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms,
having stress-induced activation and feedback regulations with multiple partners, the HSR is still
incompletely understood. In this context, we propose a minimal molecular model for the gene
regulatory network of the HSR that reproduces quantitatively different heat shock experiments both
on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics
laws, is kept with a low dimensionality without altering the biological interpretation of the model
dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of
the network. Moreover, by a steady states analysis of the network, three different temperature stress
regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal
adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes
are consequences of the titration mechanism. The simplicity of the present model is of interest in
order to study detailed modelling of cross regulation between the HSR and other major genetic
networks like the cell cycle or the circadian clock.
Sivéry, A., Courtade, E., Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Physical biology, 13(6), 066008.
2022-01-25 | MODEL2201210001 | BioModels
Project description:Because 99% of the mitochondrial proteome is encoded by the nucleus, most mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently fold into their functional state. Mitochondrial precursors are imported as unfolded polypeptides due to the limited pore size of the import machinery. For proteins of the mitochondrial matrix and inner membrane, two separate and highly conserved chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding. Here we show that LONP1, a AAA+ protease of the mitochondrial matrix, works with the mtHSP70 chaperone system to promote mitochondrial protein folding. Inhibition of LONP1 results in aggregation of a protein subset similar to that caused by knockdown of DNAJA3, a co-chaperone of mtHSP70. LONP1 is required for DNAJA3 and mtHSP70 solubility, and its ATPase, but not its protease activity, is required for this function. In vitro, LONP1 collaborates with mtHSP70 and its co-factors to stabilize a folding intermediate of OXA1L. In the absence of LONP1, the interaction of mtHSP70 with OXA1L is futile and results in substrate-induced coaggregation. Our results identify mitochondrial LONP1 as a critical factor in the mtHSP70 folding pathway and directly demonstrate its long suspected chaperone activity.
2020-12-07 | PXD021939 | Pride
Project description:It is documented that intracellular succinate levels are maintained and regulated by mitochondrial complexes II. In order to define the LONP1-dependent regulators of succinate content, unbiased TurboID-based proximity labeling was employed to exploit LONP1-targeting proteins. Our results showed that 63.5% of the proteins identified by LONP1-N-TurboID-based proximity labeling are mitochondrial proteins. Functional protein association networks analysis of the identified proteins indicated that these biotinylated proteins are related to carboxylic acid metabolic process, mitochondrial organization and mitochondrial gene expression.
2023-04-08 | PXD031197 | Pride
Project description:In this study, we have analyzed the expression profiles of rice genes under control and heat shock conditions using microarray technology to identify the genes differentially expressed. Experiment Overall Design: 14-day-old light-grown rice seedlings grown under controlled conditions and those subjected to heat shock were used for RNA extraction and hybridization on Affymetrix microarrays. Three technical replicates of each sample were used for microarray analysis. For heat shock treatment, the seedlings were kept in a chamber at 42 degree C. The seedlings kept at 28-30 degree C, served as control (Seedling).
2009-01-17 | E-GEOD-14275 | biostudies-arrayexpress