Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SILAC-based subcellular fraction of DNJAC15 and DNAJC19 knockdown in HeLa cells

ABSTRACT: Mitochondria adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limit mitochondrial fusion and promote mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 reduces the import of OXPHOS-related proteins via the TIMM23-TIMM17A protein translocase, limiting OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum and induce an ATF6-related unfolded protein response. Our results demonstrate stress-dependent changes in protein import specificity as part of the OMA1-mediated mitochondrial stress response and highlight the interdependence of proteostasis regulation between different organelles. This submission is related to: The samples are described in an accompanied Excel file.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Hendrik Nolte

LAB HEAD: Thomas Langer

PROVIDER: PXD061449 | Pride | 2025-12-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20240405_bB5l5jkrid_DoDi_01_1_samples-00-01-02_7vGQ.raw	Raw
	20240405_bB5l5jkrid_DoDi_02_2_samples-03-04-05_2c41.raw	Raw
	20240405_bB5l5jkrid_DoDi_03_3_samples-06-07-08_s0ZH.raw	Raw
	20240405_bB5l5jkrid_DoDi_04_4_samples-09-10-11_zMfG.raw	Raw
	20240405_bB5l5jkrid_DoDi_05_5_samples-12-13-14_8fw9.raw	Raw

Items per page:

1 - 5 of 47

Similar Datasets

SILAC-based subcellular fractionation (PM,Golgi,soluble) upon DNAJC15 and DNAJC19 knockdown in HeLa cells

Project description:Mitochondria adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limit mitochondrial fusion and promote mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 reduces the import of OXPHOS-related proteins via the TIMM23-TIMM17A protein translocase, limiting OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum and induce an ATF6-related unfolded protein response. Our results demonstrate stress-dependent changes in protein import specificity as part of the OMA1-mediated mitochondrial stress response and highlight the interdependence of proteostasis regulation between different organelles. This dataset contains the fractions of plasmamembrane (40kg), the golgi (100kg) and the soluble fraction. The whole cell (wc), mitochondria (mt) and mitochondria + proteinase K are available under the identifier: Check the attached Excel file for description of the samples and the SILAC channels.

2025-12-16 | PXD061185 | Pride

SILAC-based carbonate extraction of subcellular fraction ER

Project description:Mitochondria dynamically adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limit mitochondrial fusion and promote mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 impairs mitochondrial protein import and restricts OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum inducing an unfolded protein response. Our results demonstrate stress-dependent changes in mitochondrial protein import as part of the OMA1-mediated mitochondrial stress response and highlight the interdependence of proteostasis regulation between different organelles. In this dataset, we aimed to identifiy were mitochondrial proteins are localized when they cannot be imported into mitochondrial at given rate.

2025-12-19 | PXD070854 | Pride

Transcriptomics DNAJC15 and DNAJC19 knockdown in HeLa cells

Project description:To better understand how OMA1 affects mitochondrial proteostasis and stress responses, we performed a proteomic survey of OMA1-deficient cells for proteolytic substrates. We demonstrate that OMA1 cleaves the mitochondrial chaperone DNAJC15 facilitating its degradation by the mitochondrial m-AAA protease. The loss of DNAJC15 alters protein import by TIM23 protein translocases in the IM and limits the accumulation of OXPHOS-related mitochondrial matrix and IM proteins. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum (ER) and trigger an ATF6-related unfolded protein response. These results demonstrate that OMA1 allows to adapt mitochondrial protein biogenesis to stress and reveal an intricate network of cellular stress responses to proteostasis disturbances.

2025-12-19 | GSE299431 | GEO

DNAJC15 endog. interactome DSP-aided in WT and AFG3L2-KO HeLa cells

Project description:Mitochondria dynamically adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limits mitochondrial fusion and promotes mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 impairs mitochondrial protein import and restricts OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum inducing an unfolded protein response. Our results demonstrate stress-dependent changes in mitochondrial protein import as part of the OMA1-mediated mitochondrial stress response and highlight the interdependence of proteostasis regulation between different organelles. In this part of the project, the interactome of the short-JC15 (cleaved by OMA1) was explored. In AFG3L2 there is an increased accumulation of s-JC15. The endougenously JC15 was pulled down. DSP was used to cross-link proteins prior to pulldown. The internal ID is RzrI9DIje2. Due to character restrictions, the raw files had to be renamed for upload replacing (--) to KO and (++) to WT.

2025-12-16 | PXD070836 | Pride

TIMM17A and TIMM17B knockdown in DNAJC15 knockout HeLa cells

Project description:To understand how OMA1 affects mitochondrial proteostasis and stress responses, we performed a proteomic survey of OMA1-deficient cells for proteolytic substrates. We demonstrate that OMA1 cleaves the mitochondrial chaperone DNAJC15 facilitating its degradation by the mitochondrial m-AAA protease. The loss of DNAJC15 alters protein import by TIM23 protein translocases in the IM and limits the accumulation of OXPHOS-related mitochondrial matrix and IM proteins. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum (ER) and trigger an ATF6-related unfolded protein response. These results demonstrate that OMA1 allows to adapt mitochondrial protein biogenesis to stress and reveal an intricate network of cellular stress responses to proteostasis disturbances.

2025-12-19 | PXD061131 | Pride

Complex II assembly drives metabolic adaptation to OXPHOS dysfunction.

Project description:During acute oxidative phosphorylation (OXPHOS) dysfunction, the reverse activity of succinate dehydrogenase (Complex II) maintains the redox state of the Coenzyme Q pool by utilizing either fumarate or oxygen as terminal electron acceptors. The tendency for one over another has been suggested to be tissue specific. We identified the action of SDHAF2 protein, a Complex II assembly factor that enhances the flavination of catalytic subunit SDHA, as critical for metabolic adaptation during Complex III dysfunction in HEK293T cells. Loss of SDHAF2 during Complex III inhibition led to a net reductive TCA cycle from loss of succinate oxidation, loss of SDHA active site derived reactive oxygen species (ROS)-signaling, insufficient adaptation to glycolysis, and a severe growth impairment. Cell lines adapted to glycolysis did not accumulate SDHAF2 upon Coenzyme Q-pool stress, exhibited a net reductive TCA cycle and mild growth phenotypes with or without SDHAF2 being present. Thus, our study reveals how Complex II assembly controls a balance between dynamics of TCA cycle directionality, protection from Q-pool stress, and an ability to utilize ROS-meditated signaling to overcome acute OXPHOS dysfunction in cells reliant on mitochondrial respiration.

2025-06-06 | PXD064675 | Pride

Mouse heart proteomics in Oma1 and Cox10 deficient mice

Project description:Cardiomyopathy and heart failure are common manifestations in mitochondrial disease caused by deficiencies in the oxidative phosphorylation system of mitochondria (OXPHOS). Here, we demonstrate that the cardiac-specific loss of the assembly factor Cox10 of the cytochrome c oxidase causes mitochondrial cardiomyopathy in mice, which is associated with OXPHOS deficiency, lysosomal defects and an aberrant mitochondrial morphology and ultrastructure. We demonstrate activation of the mitochondrial peptidase Oma1 in Cox10-/- mice, which results in mitochondrial fragmentation and induction of the integrated stress response (ISR) along the Oma1-Dele1-Atf4 signalling axis. Ablation of Oma1 or Dele1 in Cox10-/- mice aggravates cardiomyopathy. ISR inhibition impairs the cardiac glutathione metabolism, decreases the levels of the glutathione peroxidase Gpx4 and increases lipid peroxidation in the heart, ultimately culminating in ferroptosis. Our results demonstrate a protective role of the Oma1-mediated ISR in mitochondrial cardiomyopathy and link ferroptosis to OXPHOS deficiency and mitochondrial disease.

2022-07-27 | PXD031641 | Pride

Neo N termiome of Oma1 and WT knockout HeLa cells

2025-12-19 | PXD061134 | Pride

The mitochondrial protease OMA1 acts as a metabolic safeguard upon nuclear DNA damage

Project description:The metabolic plasticity of mitochondria supports cell development and differentiation and ensures cell survival under stress. The peptidase OMA1 regulates mitochondrial morphology and stress signaling and orchestrates tumorigenesis and cell fate decisions in a cell and tissue-specific manner. Here, we have used unbiased systemic approaches to demonstrate that OMA1-dependent cell fate decisions are under metabolic control. A metabolism-focus CRISPR screen combined with an integrated analysis of human expression data unraveled a protective role of OMA1 against DNA damage. Nucleotide deficiencies induced by chemotherapeutic agents promote the selective, p53-dependent apoptosis of cells lacking OMA1. The protective effect of OMA1 does not depend on OMA1 activation nor on OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells have reduced glycolytic capacity and accumulate OXPHOS proteins upon DNA damage. OXPHOS inhibition restores glycolysis and confers resistance against DNA damage. Thus, metabolic cues determine cell fate decisions by OMA1, which sheds new light on the role of OMA1 in cancerogenesis.

2023-04-04 | PXD036595 | Pride

Neo N-termiome of SPG7, AFG3L2, SPG7 AFG3L2 and WT HeLa cells

2025-12-19 | PXD061137 | Pride