ArticleeLife2023
Mitochondrial protein import clogging as a mechanism of disease.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Small molecules rescue pathogenic POLGA aggregation and restore its functions in a mouse model of PEO.EMBO molecular medicine · 2026Article
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Mass spectrometry proteomics for studying mitostasis.Protein science : a publication of the Protein Society · 2026Review
- The role of the nucleus in the control of mitochondrial precursor proteins in yeast.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial protein import stress causes lysosomal damage and progressive tissue atrophy.EMBO reports · 2026Article
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- Review
- Functions of J-domain proteins in mitochondrial protein biogenesis.Protein science : a publication of the Protein Society · 2026Review
- Reactive carbonyl species in health and chronic disease: from methylglyoxal to an integrative network of metabolic regulation.Cardiovascular diabetology · 2026Review
- USP34 attenuates cartilage degradation in temporomandibular joint osteoarthritis by ANT1-mediated mitophagy.JBMR plus · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- An allosteric network governs Tom70 conformational dynamics to coordinate mitochondrial import.Structure (London, England : 1993) · 2026Article
- The IQ-compete assay for measuring mitochondrial protein import efficiencies in living yeast cells.FEBS letters · 2026Article
- Article
- Biogenesis and function of the mitochondrial solute carrier (SLC25) family in yeast.Biological chemistry · 2025Review
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- N-terminal α-amino SUMOylation promotes phosphorylation-independent cofilin-1 translocation to the mitochondrial matrix and induces apoptosis.Nature communications · 2025Article
- Harnessing mitochondrial biogenesis to combat acute kidney injury: Current insights and futuredirections.Genes & diseases · 2025Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Mitochondrial biogenesis requires the import of >1,000 mitochondrial preproteins from the cytosol. Most studies on mitochondrial protein import are focused on the core import machinery. Whether and how the biophysical properties of substrate preproteins affect overall import efficiency is underexplored. Here, we show that protein traffic into mitochondria can be disrupted by amino acid substitutions in a single substrate preprotein. Pathogenic missense mutations in ADP/ATP translocase 1 (ANT1), and its yeast homolog ADP/ATP carrier 2 (Aac2), cause the protein to accumulate along the protein import pathway, thereby obstructing general protein translocation into mitochondria. This impairs mitochondrial respiration, cytosolic proteostasis, and cell viability independent of ANT1's nucleotide transport activity. The mutations act synergistically, as double mutant Aac2/ANT1 causes severe clogging primarily at the translocase of the outer membrane (TOM) complex. This confers extreme toxicity in yeast. In mice, expression of a super-clogger ANT1 variant led to neurodegeneration and an age-dependent dominant myopathy that phenocopy ANT1-induced human disease, suggesting clogging as a mechanism of disease. More broadly, this work implies the existence of uncharacterized amino acid requirements for mitochondrial carrier proteins to avoid clogging and subsequent disease.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.