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Review
. 2018 Sep 19;5(9):180442.
doi: 10.1098/rsos.180442. eCollection 2018 Sep.

Anastasis: recovery from the brink of cell death

Ho Man Tang  1   2 , Ho Lam Tang  3
Affiliations
Review

Anastasis: recovery from the brink of cell death

Ho Man Tang et al. R Soc Open Sci. .

Erratum in

Abstract

Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death. Programmed cell death such as apoptosis has been traditionally assumed to be an intrinsically irreversible cascade that commits cells to a rapid and massive demolition. Interestingly, recent studies have demonstrated recovery of dying cells even at the late stages generally considered immutable. Here, we examine the evidence for anastasis in cultured cells and in animals, review findings illuminating the potential mechanisms of action, discuss the challenges of studying anastasis and explore new strategies to uncover the function and regulation of anastasis, the identification of which has wide-ranging physiological, pathological and therapeutic implications.

Keywords: anastasis; apoptosis; mutagenesis; programmed cell death; reversal of apoptosis; reversal of cell death process.

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Conflict of interest statement

We have no competing interests.

Figures

Figure 1.
Figure 1.
Cell recovery after attempted late apoptosis. (a) Time-lapse live cell confocal microscopy showing reversal of apoptosis in HeLa cells. To visualize mitochondria and nucleus, cells were stained with MitoTracker (red fluorescence) and Hoechst (blue fluorescence) for confocal microscopy, respectively. Cell morphology was observed with differential interference contrast (DIC) microscopy. In healthy cells, mitochondria formed a tubular network which extended throughout the cytoplasm (i). During exposure to a cell death stimulus of 3.9% ethanol, cells displayed morphological hallmarks of apoptosis including mitochondrial fragmentation, nuclear condensation, cell shrinkage, and plasma membrane blebbing (ii–iv). After washing and incubating the apoptotic dying cells with fresh culture medium, reversal of apoptosis occurred as indicated by morphological recovery of the cells (v–vii). The original movie can be viewed in electronic supplementary material. (b) Recovery of an apoptotic cell after mitochondrial cytochrome c release to cytosol. Time-lapse live cell confocal microscopy of a HeLa cell expressing a fusion protein of cytochrome c-GFP (CytoC). Before cell death induction, cytochrome c localized in tubular mitochondria (i). During apoptosis induced by 3.9% ethanol, cytochrome c was released to cytosol (ii–v). After removal of the cell death inducer, cytosolic cytochrome c was reduced in the recovered cell (vi–xii). Merged images of cytochrome c-GFP (green fluorescence) and DIC for cell morphology (top row), and images of cytochrome c-GFP only (bottom row). White arrows indicate cytosolic signal of cytochrome c-GFP. (c) Schematic diagram of a caspase-3 biosensor fusion protein NES-DEVD-RFP-NLS (Casp3Sensor). (d) Recovery of an apoptotic cell after caspase-3 activation. Time-lapse live cell confocal microscopy of a HeLa cell expressing fusion protein of Casp3Sensor. In the healthy cell, the Casp3Sensor localized in cytosol (i). During apoptotic induction of 3.9% ethanol, the caspase-3 cleaved biosensor translocated from cytosol to nucleus (ii,iii). After removal of the death stimulus, the signal of nuclear Casp3Sensor was diminished in the recovered cell (iv–vii). Merged images of Casp3Sensor (red fluorescence) and DIC for cell morphology (top row), and images of DIC only (bottom row). Blue arrows indicate nuclear signal of Casp3Sensor. (e) Apoptotic bodies fuse to cell body during cell recovery. Time-lapse live cell DIC microscopy of a healthy HeLa cell (i), the same cell after treating with a cell death stimulus of 0.5 µM staurosporine (STS; ii,iii), and then being washed and further incubated with fresh culture medium to remove the staurosporine (iv–viii). Green and yellow arrows indicate two apoptotic bodies that fused to a cell body during recovery of the cell.
Figure 2.
Figure 2.
Proposed mechanism of anastasis during cell recovery. Upregulation of pro-survival pathways identified during anastasis interact with the apoptosis network to suppress initiated death cascade and promote cell recovery.
Figure 3.
Figure 3.
Emerging hallmarks of anastasis. This illustration encompasses the proposed features and consequences of anastasis.
See this image and copyright information in PMC

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References

    1. Kroemer G, et al. 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 16, 3–11. (10.1038/cdd.2008.150) - DOI - PMC - PubMed
    1. Galluzzi L, et al. 2012. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 19, 107–120. (10.1038/cdd.2011.96) - DOI - PMC - PubMed
    1. Galluzzi L, et al. 2018. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 25, 486–541. (10.1038/s41418-017-0012-4) - DOI - PMC - PubMed
    1. Kerr JF, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257. (10.1038/bjc.1972.33) - DOI - PMC - PubMed
    1. Jacobson MD, Weil M, Raff MC. 1997. Programmed cell death in animal development. Cell 88, 347–354. (10.1016/S0092-8674(00)81873-5) - DOI - PubMed

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