ArticleProceedings of the National Academy of Sciences of the United States of America2023
Nascent mitochondrial proteins initiate the localized condensation of cytosolic protein aggregates on the mitochondrial surface.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- Physiological implications of phase separation in vesicle organization and trafficking.BMC biology · 2026Review
- When mitochondria lose their fold: matrix proteostasis and stress signaling.Frontiers in physiology · 2026Review
- Tom70-mediated mitochondria-nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis.bioRxiv : the preprint server for biology · 2025Article
- Molecular machineries and pathways of mitochondrial protein transport.Nature reviews. Molecular cell biology · 2025Review
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
- A protein-specific priority code in presequences determines the efficiency of mitochondrial protein import.PLoS biology · 2025Article
- Protein moonlighting by a target gene dominates phenotypic divergence of the Sef1 transcriptional regulatory network in yeasts.Nucleic acids research · 2024Article
- Privileged proteins with a second residence: dual targeting and conditional re-routing of mitochondrial proteins.The FEBS journal · 2024Review
- 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
- Nascent mitochondrial proteins initiate the localized condensation of cytosolic protein aggregates on the mitochondrial surface.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Eukaryotes organize cellular contents into membrane-bound organelles and membrane-less condensates, for example, protein aggregates. An unsolved question is why the ubiquitously distributed proteins throughout the cytosol give rise to spatially localized protein aggregates on the organellar surface, like mitochondria. We report that the mitochondrial import receptor Tom70 is involved in the localized condensation of protein aggregates in budding yeast and human cells. This is because misfolded cytosolic proteins do not autonomously aggregate in vivo; instead, they are recruited to the condensation sites initiated by Tom70's substrates (nascent mitochondrial proteins) on the organellar membrane using multivalent hydrophobic interactions. Knocking out Tom70 partially impairs, while overexpressing Tom70 increases the formation and association between cytosolic protein aggregates and mitochondria. In addition, ectopic targeting Tom70 and its substrates to the vacuole surface is able to redirect the localized aggregation from mitochondria to the vacuolar surface. Although other redundant mechanisms may exist, this nascent mitochondrial proteins-based initiation of protein aggregation likely explains the localized condensation of otherwise ubiquitously distributed molecules on the mitochondria. Disrupting the mitochondrial association of aggregates impairs their asymmetric retention during mitosis and reduces the mitochondrial import of misfolded proteins, suggesting a proteostasis role of the organelle-condensate interactions.
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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 Socratic graph.