Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation

Loo, Geert; Schotte, Peter; Gurp, Maria van; Demol, Hans; Hoorelbeke, Bart; Gevaert, Kris; Rodríguez, Iván; Ruiz-Carrillo, Adolfo; Vandekerckhove, Joël; Declercq, Wim; Beyaert, Rudi; Vandenabeele, Peter

doi:10.1038/sj.cdd.4400944

Cited by 300 publications

(213 citation statements)

References 23 publications

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“…As previously described, some of the events thought to significantly contribute to the pathophysiological changes following acute SCI include disruption of the mitochondrial inner membrane potential and formation of the mPTP, leading to mPT and cell death via necrosis [83][84][85][86], as well as programmed cell death mechanisms [87][88][89][90][91][92][93]. Therefore, promoting mitochondrial function by limiting mPTP formation and subsequent mPT may have significant therapeutic benefits for the treatment of acute SCI.…”

Section: Targeting the Mptp In Acute Scimentioning

confidence: 99%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

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Section: Targeting the Mptp In Acute Scimentioning

confidence: 99%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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“…21,22 We found that AIF continued to remain in the mitochondrial compartment upon neurodegenerative stimuli in ETNA cells 72 h after G93A-SOD1 transfection or 96 h after Ab application (Figure 6a, b), both in the presence and absence of apoptosome. Similarly, when cytochrome c was released in ETNA cells, the Endonuclease G (EndoG), a factor also known to trigger a caspase-independent type of death, 23 was retained in the mitochondria and did not contribute to any delayed forms of cell death ( Figure 6c). Release of both AIF and EndoG from ETNA À/À cells mitochondria remain intact after cytochrome c release induced by neurodegenerative stimuli…”

Section: Etna Cells Apoptosis Induced By Neurodegenerative Stimuli Ismentioning

confidence: 99%

Apoptosome inactivation rescues proneural and neural cells from neurodegeneration

et al. 2004

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Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1 À/À embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1 À/À NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1 À/À NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-b peptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1 À/À primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.

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“…EndoG is localized in the mitochondria, and then translocates to the nucleus during apoptosis with cell death stimuli such as truncated Bid (tBid), tumor-necrosis factor-alpha (TNF-a) and UV irradiation. 6,7 Thus, EndoG joins other mitochondrial proteins including cytochrome c, Omi/ HtrA2, Smac/DIABLO and apoptosis-inducing factor (AIF) as cell death effectors that are sequestered in the mitochondria, but released during the cell death process. However, the exact role and relevance of EndoG in apoptosis is controversial.…”

Section: Introductionmentioning

confidence: 99%

EndoG is dispensable in embryogenesis and apoptosis

Sasaki

et al. 2005

Cell Death Differ

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The mitochondrial protein, endonuclease G (EndoG), is one of the endonucleases implicated in DNA fragmentation during apoptosis. It has been shown to translocate from the mitochondria to the nucleus upon cell death stimuli. These observations suggest that EndoG is a mitochondrial cell death effector, and that it possibly acts as a cell death nuclease, similar to DNA fragmentation factor. To better understand the role of EndoG in development and apoptosis, we generated EndoG null mice by homologous gene targeting without disruption of D2Wsu81e. EndoG null mice are viable and develop to adulthood with no obvious abnormalities. Fibroblasts generated from the EndoG null mice show no difference in susceptibility when induced to die by a variety of intrinsic and extrinsic apoptotic stimuli. Additionally, EndoG null mice are equally sensitive to excitotoxic stress. These data suggest that EndoG is not essential for early embryogenesis and apoptosis.

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Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation

Cited by 300 publications

References 23 publications

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

Apoptosome inactivation rescues proneural and neural cells from neurodegeneration

EndoG is dispensable in embryogenesis and apoptosis

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