Living with death: the evolution of the mitochondrial pathway of apoptosis in animals

Oberst, Andrew; Bender, Cheryl E.; Green, Douglas R.

doi:10.1038/cdd.2008.65

Cited by 191 publications

(135 citation statements)

References 77 publications

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“…The absence of an overt phenotype in the CypD/RIPK3-dko mice contrasts with the early lethality and tumor susceptibility usually seen in mutant mice lacking major central pathways of apoptosis (16,47,48) and indicates the predominant involvement of RN mechanisms in severe stress and injury settings as opposed to the physiologic role of apoptosis during development, adult tissue remodeling, and immune system regulation. A similar distinction holds true for at least two of the other RN pathways, pyroptosis (31) and parthanatos (49), because caspase-11-deficient mice that do not undergo pyroptosis and PARP1-deficient mice that do not undergo parthanatos are also viable and fertile.…”

Section: Discussionmentioning

confidence: 77%

Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Linkermann

Bräsen

Darding

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

502

456

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Regulated necrosis (RN) may result from cyclophilin (Cyp)D-mediated mitochondrial permeability transition (MPT) and receptorinteracting protein kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways exist. Here, we demonstrate that necroptosis in ischemia-reperfusion injury (IRI) in mice occurs as primary organ damage, independent of the immune system, and that mice deficient for RIPK3, the essential downstream partner of RIPK1 in necroptosis, are protected from IRI. Protection of RIPK3-knockout mice was significantly stronger than of CypD-deficient mice. Mechanistically, in vivo analysis of cisplatin-induced acute kidney injury and hyperacute TNF-shock models in mice suggested the distinctness of CypD-mediated MPT from RIPK1/RIPK3-mediated necroptosis. We, therefore, generated CypD-RIPK3 double-deficient mice that are viable and fertile without an overt phenotype and that survived prolonged IRI, which was lethal to each single knockout. Combined application of the RIPK1 inhibitor necrostatin-1 and the MPT inhibitor sanglifehrin A confirmed the results with mutant mice. The data demonstrate the pathophysiological coexistence and corelevance of two separate pathways of RN in IRI and suggest that combination therapy targeting distinct RN pathways can be beneficial in the treatment of ischemic injury.RIP3 | RIP1 | programmed necrosis | apoptosis

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Section: Discussionmentioning

confidence: 77%

Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Linkermann

Bräsen

Darding

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

502

456

View full text Add to dashboard Cite

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“…Apoptosis, by morphological criteria, has unambiguously been described throughout the animals, including Sponges, Cnidaria, Platyhelminthes, Mollusks, Nematodes, Arthropods, Echinoderms, and Chordates, both invertebrate (Ciona) and vertebrate (5). In addition to the C. elegans and Drosophila homologs, homologs of caspases are described in many of these other phyla, as are Bcl-2 homologs (Table S1).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial pathway of apoptosis is ancestral in metazoans

Bender

Fitzgerald

Tait

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

106

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The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome c , which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. Here we show that apoptosis in a lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and that cytochrome c triggers caspase activation in cytosolic extracts from these animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate MOMP. These results suggest that the mitochondrial pathway of apoptosis in animals predates the emergence of the vertebrates but was lost in some lineages (e.g., nematodes). In further support of this hypothesis, we surveyed the ability of cytochrome c to trigger caspase activation in cytosolic extracts from a variety of organisms and found this effect in cytosolic extracts from invertebrate deuterostomes (phylum Echinodermata).

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“…Some investigators suggested that the mitochondrial 'amplification loop' has been added to the 'core' machinery during the evolution of higher animals. 11 However, another plausible scenario predicts that the link between mitochondrial stress, cytochrome c release and apoptosis induction that regulates intrinsic apoptosis in mammals (and presumably also in a variety of primitive animals including mollusks) 14 has been deleted during the evolution of nematodes (which at the adult stage are mainly composed of post-mitotic cells and hence cannot afford a stress-induced apoptotic default pathway). 15,16 Irrespective of these speculative considerations, it is clear that the pioneering work on C. elegans cell death has inspired the field of mammalian cell death research, especially during the 1980s and the 1990s.…”

Section: The 'Core' Machinery For Cell Death Executionmentioning

confidence: 99%

Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery

2009

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Lethal mitochondrial membrane permeabilization has been depicted as the result of two fundamentally distinct processes, namely primary mitochondrial outer membrane permeabilization (MOMP) versus permeability transition (PT) ignited at the level of the mitochondrial inner membrane. MOMP and PT have been connected to apoptosis and necrosis, respectively. Moreover, it has been thought that MOMP was mediated by pro-apoptotic multidomain proteins of the Bcl-2 family (Bax and Bak), which would operate near-to-independently from the permeability transition pore complex (PTPC) composed by voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT) and cyclophilin D. A recent paper in Molecular and Cellular Biology now reveals the obligate contribution of one particular ANT isoform to the execution of developmental and homeostatic cell death in Caenorhabditis elegans. The physical and functional interaction between CED-9, the sole multidomain Bcl-2 protein of C. elegans, and ANT emphasizes the existence of an intricate, phylogenetically conserved crosstalk between Bcl-2 family proteins and constituents of the PTPC. In this issue of Cell Death and Differentiation, Malorni et al. further corroborate this notion by showing that type 2 transglutaminase (TG2) is essential for the correct assembly/function of ANT1, and that, at least in some experimental settings, TG2 might be required to enable and/or stabilize the pro-apoptotic association of Bax with ANT1. The 'core' machinery of apoptosis was discovered by screening Caenorhabditis elegans mutations that suppressed developmental cell death, yielding a number of genes whose mammalian equivalents also have an important function in physiological and disease-associated apoptosis. Once it has been transcriptionally upregulated, EGL-1 (the only BH3-only protein encoded by C. elegans) disrupts a molecular complex composed by CED-9 (a Bcl-2 ortholog localized in mitochondrial membranes) and CED-4 (the nematode counterpart of Apaf-1, which is also normally present at mitochondria). As a consequence, CED-4 becomes free to translocate to the nuclear envelope and to activate CED-3 (the worm caspase), thereby inducing apoptosis. 1,2 Now, a new protein, WAN-1, the nematode ortholog of mammalian adenine nucleotide translocase (ANT) has been added to the 'core' machinery. 3 The 'Core' Machinery for Cell Death ExecutionThe scenario of a conserved cell death 'core' machinery composed by EGL-1, CED-9, CED-4 and CED-3 has been dominating the field of cell death research up to the point that some investigators suggested the existence of a ternary molecular complex made by Apaf-1, caspase-9 and the Bcl-2 homolog Bcl-X L also in mammalian cells, 4,5 which turned out to be a bold artifact. [6][7][8] Similarly, the idea that EGL-1, CED-9, CED-4 and CED-3 might have other functions than mediating cell death (EGL-1 as an inducer of autophagy, 9 CED-4 as part of the intra-S-phase DNA damage checkpoint, 2 CED-3 in the innate immune system 10 ) met incredulity and resistance. Prominent ...

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Living with death: the evolution of the mitochondrial pathway of apoptosis in animals

Cited by 191 publications

References 77 publications

Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Mitochondrial pathway of apoptosis is ancestral in metazoans

Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery

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