SILAC-based subcellular fractionation (PM,Golgi,soluble) upon DNAJC15 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 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Hendrik Nolte  

LAB HEAD: Thomas Langer

PROVIDER: PXD061185 | Pride | 2025-12-16

REPOSITORIES: Pride