ArticleThe EMBO journal2021
Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Methods to Study Mitochondrial Metabolism and Homeostasis in Fission Yeast.Yeast (Chichester, England) · 2026Review
- The role of the nucleus in the control of mitochondrial precursor proteins in yeast.Protein science : a publication of the Protein Society · 2026Review
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial presequences are more than just address labels.Protein science : a publication of the Protein Society · 2026Review
- Molecular machineries and pathways of mitochondrial protein transport.Nature reviews. Molecular cell biology · 2025Review
- Mitochondrial protein import stress augments α-synuclein aggregation and neural damage independent of bioenergetics.Research square · 2025Article
- A protein-specific priority code in presequences determines the efficiency of mitochondrial protein import.PLoS biology · 2025Article
- Article
- CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates.Molecules (Basel, Switzerland) · 2025Review
- Mitofusin 2 displays fusion-independent roles in proteostasis surveillance.Nature communications · 2025Article
- Mitochondrial protein import stress.Nature cell biology · 2025Review
- Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation.Nature aging · 2023Article
- Adenine nucleotide carrier protein dysfunction in human disease.IUBMB life · 2023Review
- MitoStores: chaperone-controlled protein granules store mitochondrial precursors in the cytosol.The EMBO journal · 2023Article
- The Journey of Mitochondrial Protein Import and the Roadmap to Follow.International journal of molecular sciences · 2023Review
- The [PSIMolecular biology of the cell · 2022Article
- Long-term mitochondrial stress induces early steps of Tau aggregation by increasing reactive oxygen species levels and affecting cellular proteostasis.Molecular biology of the cell · 2022Article
- Expression of Huntingtin and TDP-43 Derivatives in Fission Yeast Can Cause Both Beneficial and Toxic Effects.International journal of molecular sciences · 2022Article
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19 authors at 7 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how mitochondrial processes regulate the behavior of aggregation-prone polyQ protein derived from human huntingtin. Expression of Q97-GFP rapidly led to insoluble cytosolic aggregates and cell death. Although aggregation impaired mitochondrial respiration only slightly, it considerably interfered with the import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97-GFP, whereas Mia40 overexpression strongly suppressed the formation of toxic Q97-GFP aggregates both in yeast and in human cells. Based on these observations, we propose that the post-translational import of mitochondrial precursor proteins into mitochondria competes with aggregation-prone cytosolic proteins for chaperones and proteasome capacity. Mia40 regulates this competition as it has a rate-limiting role in mitochondrial protein import. Therefore, Mia40 is a dynamic regulator in mitochondrial biogenesis that can be exploited to stabilize cytosolic proteostasis.
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