Proteomics

Dataset Information

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Cycloheximide time course in WT and AFG3L2 knockout HeLa cells


ABSTRACT: Mitochondria are metabolically rewired in hypoxia when cells switch to glycolytic growth. In addition to the well-established role of transcriptional and translational programs, there is increasing evidence that post-translational mechanisms contribute to the rapid adaptation of the mitochondrial proteome to hypoxia. Here, we have used a proteomic survey to define how the m-AAA protease AFG3L2, a proteolytic complex in the inner mitochondrial membrane, regulates mitochondrial proteostasis. Our experiments identify a broad spectrum of mitochondrial substrate proteins and show that AFG3L2 is activated in hypoxia along an HIF1-mTORC1 signaling axis. AFG3L2-mediated proteolysis restricts mitochondrial biogenesis and gene expression by degrading proteins, which are involved in mitochondrial protein import, mitochondrial transcription, mRNA processing, modification and stability, and RNA granule formation. Our experiments highlight the important contribution of proteolytic rewiring of the mitochondrial proteome for the adaptation to low oxygen tension and shed new light on the pathophysiology of several neurodegenerative disorders associated with mutations in AFG3L2. This dataset is part of a collection of different datasets of the above-mentioned project. Here we studied the protein degradation in HeLa cells in conditions where translation is blocked using cycloheximide. Please note that there is a file describing (0069_SampleNames) that indicates the raw file - sample matching table but also indicates if a sample has been excluded because it did not pass the quality control standards (for example number of proteins quantified). Please note that also SPG7KO and AFG3L2 and SPG7 double KO were measured in this project, but are not part of the paper.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Hendrik Nolte  

LAB HEAD: Thomas Langer

PROVIDER: PXD056318 | Pride | 2026-01-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
0069_SEARCH.zip Other
0069_SampleNames.xlsx Xlsx
20200130_DD_0069_YvLa_ChxChase_sample_01.raw Raw
20200130_DD_0069_YvLa_ChxChase_sample_02.raw Raw
20200130_DD_0069_YvLa_ChxChase_sample_03.raw Raw
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