TIMM17A and TIMM17B knockdown in DNAJC15 knockout HeLa cells
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ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Epithelial Cell, Cell Culture
SUBMITTER: 
Hendrik Nolte
LAB HEAD: Thomas Langer
PROVIDER: PXD061131 | Pride | 2025-12-19
REPOSITORIES: Pride
Dataset's files
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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
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.
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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. In this dataset, we investigated the Neo-N terminal of proteins dependent on Oma1. In the original publication, only Oma1 and WT were utilized, while this dataset also contains MICS1 knockout and Oligomycin treatment.
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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. In this dataset, we determined the Neo N termiome of SPG7, AFG3L2 and SPG7 AFG3L2 knock out HeLa cells. The project is related to other identfiers PXD061131, PXD061134.
2025-12-19 | PXD061137 | Pride
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.
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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 submission is related to: The samples are described in an accompanied Excel file.
2025-12-16 | PXD061449 | Pride
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.
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Project description:Mutations in CHCHD10, a mitochondrial protein implicated in proteostasis and cristae maintenance, cause autosomal dominant mitochondrial diseases characterized by cardiomyopathy and neurodegeneration. Heterozygous Chchd10 S55L knock-in mice (modeling the human S59L variant) develop progressive mitochondrial cardiomyopathy driven by CHCHD10 aggregation, which is associated with chronic activation of the mitochondrial integrated stress response (mtISR). Here, we demonstrate that cardiac dysfunction is affected by biological sex and is associated with dual defects originating at the onset of disease: (1) early respiratory chain failure linked to cytochrome c depletion and impaired copper homeostasis and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis. Genetic inactivation of OMA1 delays cardiomyopathy without rescuing CHCHD10 insolubility, proteomic remodeling, cristae defects or OXPHOS impairment, demonstrating that mtISR can be uncoupled from the bioenergetic collapse triggered by CHCHD10 protein aggregation. Proteomic profiling of soluble and insoluble mitochondrial proteins reveals wide-spread disruptions of mitochondrial proteostasis, including IMS proteins involved in cytochrome c biogenesis. Defective respiration in mutant mitochondria could be rescued by the exogenous addition of cytochrome c, pinpointing IMS proteostasis disruption as a key pathogenic mechanism. Our work reveals that CHCHD10 insolubility and aggregation compromises metabolic resilience by impairing both electron transport and stress adaptation within the IMS, offering new perspectives for the development of therapeutic targets. This repository contains the heart whole proteome of the four different genotypes. a) whole proteome dataset is indicated by the identifier: KmUUbGabck
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Project description:Mutations in CHCHD10, a mitochondrial protein implicated in proteostasis and cristae maintenance, cause autosomal dominant mitochondrial diseases characterized by cardiomyopathy and neurodegeneration. Heterozygous Chchd10 S55L knock-in mice (modeling the human S59L variant) develop progressive mitochondrial cardiomyopathy driven by CHCHD10 aggregation, which is associated with chronic activation of the mitochondrial integrated stress response (mtISR). Here, we demonstrate that cardiac dysfunction is affected by biological sex and is associated with dual defects originating at the onset of disease: (1) early respiratory chain failure linked to cytochrome c depletion and impaired copper homeostasis and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis. Genetic inactivation of OMA1 delays cardiomyopathy without rescuing CHCHD10 insolubility, proteomic remodeling, cristae defects or OXPHOS impairment, demonstrating that mtISR can be uncoupled from the bioenergetic collapse triggered by CHCHD10 protein aggregation. Proteomic profiling of soluble and insoluble mitochondrial proteins reveals wide-spread disruptions of mitochondrial proteostasis, including IMS proteins involved in cytochrome c biogenesis. Defective respiration in mutant mitochondria could be rescued by the exogenous addition of cytochrome c, pinpointing IMS proteostasis disruption as a key pathogenic mechanism. Our work reveals that CHCHD10 insolubility and aggregation compromises metabolic resilience by impairing both electron transport and stress adaptation within the IMS, offering new perspectives for the development of therapeutic targets. This repository is connected to PXD064045. The internal idetnfier is: DECTXuxSGj Please note that we had to rename the raw file containing ++ and +- to WT and HET, respectively due to character contstrains in PRIDE submission.
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