Lima 2021 Nat Metab

Lima A, Lubatti G, Burgstaller J, Hu D, Green AP, Di Gregorio A, Zawadzki T, Pernaute B, Mahammadov E, Perez-Montero S, Dore M, Sanchez JM, Bowling S, Sancho M, Kolbe T, Karimi MM, Carling D, Jones N, Srinivas S, Scialdone A, Rodriguez TA (2021) Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development. Nat Metab 3:1091-108. https://doi.org/10.1038/s42255-021-00422-7

» PMID: 34253906 Open Access

Lima A, Lubatti G, Burgstaller J, Hu D, Green AP, Di Gregorio A, Zawadzki T, Pernaute B, Mahammadov E, Perez-Montero S, Dore M, Sanchez JM, Bowling S, Sancho M, Kolbe T, Karimi MM, Carling D, Jones N, Srinivas S, Scialdone A, Rodriguez TA (2021) Nat Metab

Abstract: Cell competition is emerging as a quality-control mechanism that eliminates unfit cells in a wide range of settings from development to the adult. However, the nature of the cells normally eliminated by cell competition and what triggers their elimination remains poorly understood. In mice, 35% of epiblast cells are eliminated before gastrulation. Here we show that cells with mitochondrial defects are eliminated by cell competition during early mouse development. Using single-cell transcriptional profiling of eliminated mouse epiblast cells, we identify hallmarks of cell competition and mitochondrial defects. We demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function triggers cell competition. Moreover, we show that in the mouse embryo, cell competition eliminates cells with sequence changes in mt-Rnr1 and mt-Rnr2, and that even non-pathological changes in mitochondrial DNA sequences can induce cell competition. Our results suggest that cell competition is a purifying selection that optimizes mitochondrial performance before gastrulation.

• Bioblast editor: Gnaiger E

Correction: FADH₂ and Complex II

FADH₂ is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).

Gnaiger E (2024) Complex II ambiguities ― FADH₂ in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - »Bioblast link«

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Enzyme: Complex II;succinate dehydrogenase