ArticleBMC biology2014
An inside-out origin for the eukaryotic cell.
Article in BMC biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 211 citations in OpenAlex.
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- Quantifying the fitness contribution of phagocytosis.bioRxiv : the preprint server for biology · 2025Article
- Microcompartments in archaeal ancestors of eukaryotes: a bioenergetic engine that could have fuelled eukaryogenesis.bioRxiv : the preprint server for biology · 2025Article
- Biomolecular condensates in plant immunity.Cell host & microbe · 2025Review
- A diverse Palaeoproterozoic microbial ecosystem implies early eukaryogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Molecular and biochemical insights from natural and engineered photosynthetic endosymbiotic systems.Current opinion in chemical biology · 2025Review
- An origin for a eukaryotic lipid transfer protein fold in Asgard archaea.bioRxiv : the preprint server for biology · 2025Article
- Hypothesis that ancestral eukaryotes sexually proliferated without kinetochores or mitosis.Journal of cell science · 2025Article
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- Bioenergetics and the Evolution of Cellular Traits.Annual review of biophysics · 2025Review
- Relationship troubles at the mitochondrial level and what it might mean for human disease.Open biology · 2025Review
- Quantifying the evolutionary paths to endomembranes.Cell reports · 2025Article
- Chimeric origins and dynamic evolution of central carbon metabolism in eukaryotes.Nature ecology & evolution · 2025Article
- Reconstructing the last common ancestor of all eukaryotes.PLoS biology · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the origin of the eukaryotic cell has long been recognized as the single most profound change in cellular organization during the evolution of life on earth, this transition remains poorly understood. Models have always assumed that the nucleus and endomembrane system evolved within the cytoplasm of a prokaryotic cell.
resultsDrawing on diverse aspects of cell biology and phylogenetic data, we invert the traditional interpretation of eukaryotic cell evolution. We propose that an ancestral prokaryotic cell, homologous to the modern-day nucleus, extruded membrane-bound blebs beyond its cell wall. These blebs functioned to facilitate material exchange with ectosymbiotic proto-mitochondria. The cytoplasm was then formed through the expansion of blebs around proto-mitochondria, with continuous spaces between the blebs giving rise to the endoplasmic reticulum, which later evolved into the eukaryotic secretory system. Further bleb-fusion steps yielded a continuous plasma membrane, which served to isolate the endoplasmic reticulum from the environment.
conclusionsThe inside-out theory is consistent with diverse kinds of data and provides an alternative framework by which to explore and understand the dynamic organization of modern eukaryotic cells. It also helps to explain a number of previously enigmatic features of cell biology, including the autonomy of nuclei in syncytia and the subcellular localization of protein N-glycosylation, and makes many predictions, including a novel mechanism of interphase nuclear pore insertion.
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