ArticleNature cell biology2025
Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- Review
- Multi-omics reveals regulatory networks and critical early-warning factors for severe disease progression in diabetic patients infected with SARS-CoV-2.Frontiers in immunology · 2026Observational
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
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Authors and funding
5 authors.
Funding
Abstract
The mitochondrial proteome is remodelled to meet metabolic demands, but how metabolic cues regulate mitochondrial protein turnover remains unclear. Here we identify a conserved, nutrient-responsive mechanism in which the amino acid leucine suppresses ubiquitin-dependent degradation of outer mitochondrial membrane (OMM) proteins, stabilizing key components of the protein import machinery and expanding the mitochondrial proteome to enhance metabolic respiration. Leucine inhibits the amino acid sensor GCN2, which selectively reduces the E3 ubiquitin ligase cofactor SEL1L at mitochondria. Depletion of SEL1L phenocopies the effect of leucine, elevating OMM protein abundance and mitochondrial respiration. Disease-associated defects in leucine catabolism and OMM protein turnover impair fertility in Caenorhabditis elegans and render human lung cancer cells resistant to inhibition of mitochondrial protein import. These findings define a leucine-GCN2-SEL1L axis that links nutrient sensing to mitochondrial proteostasis, with implications for metabolic disorders and cancer.
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Registered trials
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