Dataset Information

Molecular chaperone Hsp90 supports adaptive cell size increase in response to chronic stress

ABSTRACT: Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation through a translational "rewiring stress response". We propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Manfredo Quadroni

LAB HEAD: Didier Picard

PROVIDER: PXD039672 | Pride | 2023-12-01

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20211002_124315_Maiti-13711-RPB.kit	Other
	20211004_150008_Maiti-13489-515.sne	Other
	20211004_170220_Maiti-13489-515_Report.log.txt	Txt
	20211004_170220_Maiti-13489-515_Report.setup.txt	Txt
	20211004_170220_Maiti-13489-515_Report.txt	Txt

Items per page:

1 - 5 of 40

Similar Datasets

Project description:Objective: Athletes increasingly engage in repeated sprint training that consists of repeated short all-out effort interspersed by short periods of recovery. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN), however the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle oxidative and glycolytic adaptations as compared to RSN. Methods: Healthy young men performed nine repeated sprint training sessions in three weeks. Each training session consisted in six series of six sprints in either normoxia (FiO2 = 20.9%, RSN, n = 7) or normobaric hypoxia (FiO2 = 13.6%, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomic combined to western blotting analyses. Results: We observed similar improvements in RSA and Wingate tests in both RSH and RSN groups. Proteomic analysis revealed a decrease in several proteins involved in oxidative phosphorylation (OXPHOS) in both groups and this was confirmed with western blot showing significant reductions in complexes I and V protein levels. RSN and RSH increased protein levels of the glycolytic enzyme hexokinase II, while only RSH induced a significant increase in the glucose transporter 4 (GLUT4) protein levels, suggesting superior glycolytic adaptations in response to hypoxia. This phenotype is further supported by proteomics data showing significant increase of proteins involved in glycolysis. Our proteomics data showed in the RSH group a specific increase in several S100A family proteins, among which S100A13 was the most modified, a result confirmed by western blot. S100A proteins have recently been shown to accelerate glycolytic phenotype of cancer cells by activating the protein kinase B (Akt) pathway. Our data corroborate these findings by showing in RSH group increased Akt phosphorylation as well as increased levels of proteins related to Akt downstream effects such as enhanced translation. Conclusions: Altogether our data indicate that RSH, as compared to RSN, potentiates the muscle glycolytic phenotype, possibly through the activation of S100A13 and the Akt pathway.

Project description:In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We selected the mt-tRF-LeuTAA fragment derived from a tRNA encoded by the mitochondrial genome for further investigation, as its level is reduced in the islets of diabetes-susceptible animal models, while being abundant in ß-cells. mt-tRF-LeuTAA fragment is derived from the cleavage of tRNA-LeuTAA encoded by the mitochondrial genome. We demonstrated that mt-tRF-LeuTAA acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells. We sought to investigate the downstream mechanisms activated by this fragment. To gain a comprehensive understanding, we conducted proteomic analyses on rat islets with silenced mt-tRF-LeuTAA for 72 hours. Inhibiting mt-tRF-LeuTAA led to significant differential expression of 642 proteins, cut-off adjusted p ≤ 0.05. To further investigate the cellular rearrangement associated with the inhibition of mt-tRF-LeuTAA, we conducted enrichment analysis using Gene Ontology Molecular Function terms on mass spectrometry data. At the protein level, there was a significant enrichment of mitochondrial pathways, such as oxidoreductase activity, ATPase activity, hydrogen transport, NADH dehydrogenase activity, cytochrome-c oxidase activity, and oxygen transport. To elucidate the mechanisms by which mt-tRF-LeuTAA operates, we also conducted pull-down experiments in insulin-secreting INS832/13 cells, followed by mass spectrometry using 3'-biotinylated mimic sequence oligonucleotides of mt-tRF-LeuTAA. Our analysis unveiled interactions between mt-tRF-LeuTAA and 24 proteins, meeting the criteria of a fold change ≥ 6 and an adjusted p-value ≤ 0.05. Notably, among these proteins, 13 are localized within the mitochondria and play significant roles in mitochondrial oxidative functions. Some of these key proteins include Suclg2, Nme3, Sdha, Lrpprc, and Ndufa12. Pathway enrichment analysis of the binding partners associated with the mitochondrial fragment mt-tRF-LeuTAA indicates an over-representation of signaling pathways crucial to maintaining mitochondrial metabolism. These pathways include oxidative phosphorylation (OXPHOS), ROS-induced stress responses, the tricarboxylic acid (TCA) cycle, calcium homeostasis regulation, lipid metabolism, RNA splicing, and mitochondrial import, which all contribute fundamentally to the maintenance of mitochondrial metabolism. These findings collectively provide insights into the essential mechanisms underlining the functionality of mitochondrially-encoded tRNA-derived fragments with the view to sustaining mitochondrial metabolism.

Dataset Information

Molecular chaperone Hsp90 supports adaptive cell size increase in response to chronic stress

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets