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Article ; Online: Oxidative and energetic stresses mediate beta-cell dysfunction induced by PGC-1α.

Besseiche, A / Riveline, J-P / Delavallée, L / Foufelle, F / Gautier, J-F / Blondeau, B

2017 Volume 44, Issue 1, Page(s) 45–54

Abstract: Aim: Alteration of functional beta-cell mass in adults can be programmed by adverse events during fetal life. Previously, it was demonstrated that high glucocorticoid (GC) levels during fetal life participate in this programming by inhibition of beta- ... ...

Abstract	Aim: Alteration of functional beta-cell mass in adults can be programmed by adverse events during fetal life. Previously, it was demonstrated that high glucocorticoid (GC) levels during fetal life participate in this programming by inhibition of beta-cell development. More specifically, GC levels stimulate expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), a transcriptional co-regulator of the GC receptor (GR), which per se impairs beta-cell mass and function when overexpressed. As PGC-1α is also a potent inducer of mitochondrial biogenesis, our study aimed to determine how PGC-1α modifies mitochondrial function in beta cells and how it might regulate insulin secretion. Methods: Beta-cell function was studied in mice overexpressing PGC-1α specifically in beta cells and in MIN6 cells overexpressing PGC-1α in vitro. Results: PGC-1α overexpression in beta cells in vivo leads to a reduced beta-cell mass early in fetal life, whereas PGC-1α overexpression in vitro stimulates mitochondrial biogenesis and respiratory activity without improving ATP production, while increasing oxidative stress and impairing insulin secretion in response to glucose. While oxidative stress with PGC-1α overexpression in beta cells activates AMPK, it has also been revealed that blocking such oxidative stress or AMPK activation restores insulin secretion. Conclusion: PGC-1α induces oxidative stress, which disrupts insulin secretion by AMPK activation. Thus, control of oxidative or energetic stress in beta cells may help to restore insulin secretion.
MeSH term(s)	Animals ; Insulin/metabolism ; Insulin-Secreting Cells/metabolism ; Mice ; Mice, Transgenic ; Oxidative Stress/genetics ; Oxygen Consumption/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
Chemical Substances	Insulin ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Ppargc1a protein, mouse
Language	English
Publishing date	2017-03-01
Publishing country	France
Document type	Journal Article
ZDB-ID	1315751-6
ISSN	1878-1780 ; 1262-3636 ; 0338-1684
ISSN (online)	1878-1780
ISSN	1262-3636 ; 0338-1684
DOI	10.1016/j.diabet.2017.01.007
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Zs.A 1267: Show issues

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Article ; Online: AIF-mediated caspase-independent necroptosis requires ATM and DNA-PK-induced histone H2AX Ser139 phosphorylation.

Baritaud, M / Cabon, L / Delavallée, L / Galán-Malo, P / Gilles, M-E / Brunelle-Navas, M-N / Susin, S A

Cell death & disease

2012 Volume 3, Page(s) e390

Abstract: The alkylating DNA-damage agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces a form of caspase-independent necroptosis implicating the mitochondrial flavoprotein apoptosis-inducing factor (AIF). Following the activation of PARP-1 (poly(ADP-ribose) ...

Abstract	The alkylating DNA-damage agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces a form of caspase-independent necroptosis implicating the mitochondrial flavoprotein apoptosis-inducing factor (AIF). Following the activation of PARP-1 (poly(ADP-ribose) polymerase-1), calpains, BID (BH3 interacting domain death agonist), and BAX (Bcl-2-associated X protein), the apoptogenic form of AIF (tAIF) is translocated to the nucleus where, associated with Ser139-phosphorylated histone H2AX (γH2AX), it creates a DNA-degrading complex that provokes chromatinolysis and cell death by necroptosis. The generation of γH2AX is crucial for this form of cell death, as mutation of H2AX Ser139 to Ala or genetic ablation of H2AX abolish both chromatinolysis and necroptosis. On the contrary, reintroduction of H2AX-wt or the phosphomimetic H2AX mutant (H2AX-S139E) into H2AX(-/-) cells resensitizes to MNNG-triggered necroptosis. Employing a pharmacological approach and gene knockout cells, we also demonstrate in this paper that the phosphatidylinositol-3-OH kinase-related kinases (PIKKs) ATM (ataxia telangiectasia mutated) and DNA-dependent protein kinase (DNA-PK) mediate γH2AX generation and, consequently, MNNG-induced necroptosis. By contrast, H2AX phosphorylation is not regulated by ATR or other H2AX-related kinases, such as JNK. Interestingly, ATM and DNA-PK phosphorylate H2AX at Ser139 in a synergistic manner with different kinetics of activation. Early after MNNG treatment, ATM generates γH2AX. Further, DNA-PK contributes to H2AX Ser139 phosphorylation. In revealing the pivotal role of PIKKs in MNNG-induced cell death, our data uncover a milestone in the mechanisms regulating AIF-mediated caspase-independent necroptosis.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis Inducing Factor/metabolism ; Ataxia Telangiectasia Mutated Proteins ; Caspases/metabolism ; Cell Cycle Proteins/antagonists & inhibitors ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromatin/metabolism ; DNA Breaks, Double-Stranded/drug effects ; DNA-Activated Protein Kinase/antagonists & inhibitors ; DNA-Activated Protein Kinase/metabolism ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/metabolism ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Histones/genetics ; Histones/metabolism ; Kinetics ; Methylnitronitrosoguanidine/pharmacology ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/metabolism ; Tumor Suppressor Proteins/antagonists & inhibitors ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Apoptosis Inducing Factor ; Cell Cycle Proteins ; Chromatin ; DNA-Binding Proteins ; GTPase-Activating Proteins ; H2AX protein, mouse ; Histones ; Ralbp1 protein, mouse ; Tumor Suppressor Proteins ; Methylnitronitrosoguanidine (12H3O2UGSF) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Atm protein, mouse (EC 2.7.11.1) ; DNA-Activated Protein Kinase (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2012-09-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/cddis.2012.120
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Article ; Online: BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation.

Cabon, L / Galán-Malo, P / Bouharrour, A / Delavallée, L / Brunelle-Navas, M-N / Lorenzo, H K / Gross, A / Susin, S A

Cell death and differentiation

2011 Volume 19, Issue 2, Page(s) 245–256

Abstract: Alkylating DNA-damage agents such as N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) trigger necroptosis, a newly defined form of programmed cell death (PCD) managed by receptor interacting protein kinases. This caspase-independent mode of cell death ... ...

Abstract	Alkylating DNA-damage agents such as N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) trigger necroptosis, a newly defined form of programmed cell death (PCD) managed by receptor interacting protein kinases. This caspase-independent mode of cell death involves the sequential activation of poly(ADP-ribose) polymerase-1 (PARP-1), calpains, BAX and AIF, which redistributes from mitochondria to the nucleus to promote chromatinolysis. We have previously demonstrated that the BAX-mediated mitochondrial release of AIF is a critical step in MNNG-mediated necroptosis. However, the mechanism regulating BAX activation in this PCD is poorly understood. Employing mouse embryonic knockout cells, we reveal that BID controls BAX activation in AIF-mediated necroptosis. Indeed, BID is a link between calpains and BAX in this mode of cell death. Therefore, even if PARP-1 and calpains are activated after MNNG treatment, BID genetic ablation abolishes both BAX activation and necroptosis. These PCD defects are reversed by reintroducing the BID-wt cDNA into the BID(-/-) cells. We also demonstrate that, after MNNG treatment, BID is directly processed into tBID by calpains. In this way, calpain non-cleavable BID proteins (BID-G70A or BID-Δ68-71) are unable to promote BAX activation and necroptosis. Once processed, tBID localizes in the mitochondria of MNNG-treated cells, where it can facilitate BAX activation and PCD. Altogether, our data reveal that, as in caspase-dependent apoptosis, BH3-only proteins are key regulators of caspase-independent necroptosis.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis Inducing Factor/metabolism ; Apoptosis Regulatory Proteins/metabolism ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Bcl-2-Like Protein 11 ; Calpain/metabolism ; Caspases/metabolism ; Cell Survival/drug effects ; DNA Damage ; Embryo, Mammalian/cytology ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Lentivirus/genetics ; Membrane Proteins/metabolism ; Methylnitronitrosoguanidine/pharmacology ; Mice ; Models, Biological ; Necrosis ; Poly(ADP-ribose) Polymerases/metabolism ; Proto-Oncogene Proteins/metabolism ; Transduction, Genetic ; bcl-2-Associated X Protein/metabolism ; bcl-Associated Death Protein/metabolism
Chemical Substances	Apoptosis Inducing Factor ; Apoptosis Regulatory Proteins ; BH3 Interacting Domain Death Agonist Protein ; Bcl-2-Like Protein 11 ; Bcl2l11 protein, mouse ; Membrane Proteins ; Proto-Oncogene Proteins ; bcl-2-Associated X Protein ; bcl-Associated Death Protein ; Methylnitronitrosoguanidine (12H3O2UGSF) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Calpain (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2011-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/cdd.2011.91
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Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Kinoid of human tumor necrosis factor-alpha for rheumatoid arthritis.

Semerano, Luca / Assier, Eric / Delavallée, Laure / Boissier, Marie-Christophe

Expert opinion on biological therapy

2011 Volume 11, Issue 4, Page(s) 545–550

Abstract: Introduction: Anti-TNF-α drugs have dramatically changed treatment of rheumatoid arthritis (RA) in terms of both clinical control and articular damage prevention. Despite this, they hold some important drawbacks, such as frequent therapeutic failures ... ...

Abstract	Introduction: Anti-TNF-α drugs have dramatically changed treatment of rheumatoid arthritis (RA) in terms of both clinical control and articular damage prevention. Despite this, they hold some important drawbacks, such as frequent therapeutic failures and high costs. Anti-TNF-α active immunization, with a therapeutic vaccine against TNF-α, is a promising alternative anti-TNF-α targeting strategy, potentially devoid of treatment limitations of some of current anti-TNF blocking agents. Areas covered: This review covers the preclinical proof-of-concept of anti-TNF-α vaccination with the kinoid of human TNF-α (TNFK) and analyzes the body of evidence forming the rationale for the application of this strategy in RA and other TNF-α-dependent diseases. We describe the theoretical bases of anti-TNF-α active immunization and of experimental data supporting the applicability of TNFK to human disease in terms of both safety and efficacy. Expert opinion: Based on preclinical efficacy and safety data supporting its feasibility in a Phase I - II trial in Crohn's disease, anti-TNF-α vaccination with TNFK has entered the phase of clinical development and promises to be a valuable anti-TNF-α targeting strategy in human disease. The focus is made in the first clinical trial in RA (Phase II) on the efficacy in active RA patients having developed antibodies against anti-TNF mAbs.
MeSH term(s)	Animals ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/pharmacokinetics ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/immunology ; Humans ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Vaccines/adverse effects ; Vaccines/pharmacokinetics ; Vaccines/therapeutic use
Chemical Substances	Antirheumatic Agents ; Tumor Necrosis Factor-alpha ; Vaccines
Language	English
Publishing date	2011-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1517/14712598.2011.566856
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Zs.A 6094: Show issues

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Article ; Online: Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-α immunotherapy in human TNF-α transgenic mice depends on anti-TNF-α antibody levels.

Semerano, L / Biton, J / Delavallée, L / Duvallet, E / Assier, E / Bessis, N / Bernier, E / Dhellin, O / Grouard-Vogel, G / Boissier, M-C

Clinical and experimental immunology

2013 Volume 172, Issue 1, Page(s) 54–62

Abstract: Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of ... ...

Abstract	Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-α antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0-15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0-4); PBS. Animals were killed at week 16. Anti-hTNF-α antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-α antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0·001) and correlated inversely with histological inflammation (R = -0·78; P = 0·0001) and destruction (R = -0·67; P = 0·001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0·05). A receiver operating characteristic (ROC) analysis of anti-hTNF-α antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0·05). In a model of TNF-α-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-α antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-α antibody production. These results are relevant for future development of active anti-TNF-α immunization in human disease.
MeSH term(s)	Animals ; Antibodies/administration & dosage ; Antibodies/immunology ; Antibodies/metabolism ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/immunology ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/immunology ; Antirheumatic Agents/metabolism ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/pathology ; Cartilage, Articular/drug effects ; Cartilage, Articular/immunology ; Cartilage, Articular/pathology ; Drug Combinations ; Immunization, Passive ; Immunotherapy, Active ; Infliximab ; Male ; Mice ; Mice, Transgenic ; ROC Curve ; Tumor Necrosis Factor-alpha/administration & dosage ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/immunology ; Vaccination
Chemical Substances	Antibodies ; Antibodies, Monoclonal ; Antirheumatic Agents ; Drug Combinations ; Tumor Necrosis Factor-alpha ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2013-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1111/cei.12040
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Zs.B 337: Show issues

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Article ; Online: Early and long-lasting protection from arthritis in tumour necrosis factor alpha (TNFalpha) transgenic mice vaccinated against TNFalpha.

Delavallée, L / Le Buanec, H / Bessis, N / Assier, E / Denys, A / Bizzini, B / Zagury, D / Boissier, M-C

Annals of the rheumatic diseases

2008 Volume 67, Issue 9, Page(s) 1332–1338

Abstract: Objective: To evaluate the effect in mice with arthritis of active anti-tumour necrosis factor (TNF)alpha immunotherapy based on a keyhole limpet haemocyanin-human TNFalpha heterocomplex (hTNFalpha kinoid or TNFK) adjuvanted in incomplete Freund ... ...

Abstract	Objective: To evaluate the effect in mice with arthritis of active anti-tumour necrosis factor (TNF)alpha immunotherapy based on a keyhole limpet haemocyanin-human TNFalpha heterocomplex (hTNFalpha kinoid or TNFK) adjuvanted in incomplete Freund adjuvant. Immunotherapy was evaluated also with methotrexate. Methods: Human TNFalpha-transgenic mice received TNFK with or without methotrexate. Follow-up ranged from 6 weeks (short term) to 17 weeks (long term). Arthritis was evaluated clinically and histologically. Monitoring included titration of anti-hTNFalpha antibodies by ELISA and neutralisation assay. Results: Vaccination with TNFK was associated with rapid-onset, long-lasting protection. Long-term results showed significantly milder arthritis in vaccinated animals than in control animals at the peak of the disease. Vaccination was followed by resolution of the clinical evidence of arthritis, contrasting with severe progressive arthritis in the control group. Histological improvements with decreased inflammation and destruction were noted in all immunised groups, even after the shortest follow-up (6 weeks). High titres of neutralising anti-hTNFalpha antibodies were detected as early as the fifth week post immunisation and persisted over time. Methotrexate given concomitantly with the vaccine did not influence either the effect on arthritis or the anti-hTNFalpha antibody titres. Conclusion: Anti-cytokine induction of autoimmune protection against chronic hTNFalpha overproduction is an efficient alternative to TNFalpha blockade in experimental arthritis and can be achieved using a TNFK vaccine.
MeSH term(s)	Animals ; Arthritis, Experimental/immunology ; Arthritis, Experimental/pathology ; Arthritis, Experimental/prevention & control ; Autoantibodies/biosynthesis ; Hemocyanins ; Immunosuppressive Agents/therapeutic use ; Immunotherapy/methods ; Male ; Methotrexate/therapeutic use ; Mice ; Mice, Transgenic ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/immunology ; Vaccination/methods
Chemical Substances	Autoantibodies ; Immunosuppressive Agents ; Tumor Necrosis Factor-alpha ; Hemocyanins (9013-72-3) ; keyhole-limpet hemocyanin (FV4Y0JO2CX) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2008-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard.2007.079137
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Article ; Online: Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus.

Molecular metabolism

2020 Volume 40, Page(s) 101027

Abstract: Objectives: Apoptosis-Inducing Factor (AIF) is a protein involved in mitochondrial electron transport chain assembly/stability and programmed cell death. The relevant role of this protein is underlined because mutations altering mitochondrial AIF ... ...

Abstract	Objectives: Apoptosis-Inducing Factor (AIF) is a protein involved in mitochondrial electron transport chain assembly/stability and programmed cell death. The relevant role of this protein is underlined because mutations altering mitochondrial AIF properties result in acute pediatric mitochondriopathies and tumor metastasis. By generating an original AIF-deficient mouse strain, this study attempted to analyze, in a single paradigm, the cellular and developmental metabolic consequences of AIF loss and the subsequent oxidative phosphorylation (OXPHOS) dysfunction. Methods: We developed a novel AIF-deficient mouse strain and assessed, using molecular and cell biology approaches, the cellular, embryonic, and adult mice phenotypic alterations. Additionally, we conducted ex vivo assays with primary and immortalized AIF knockout mouse embryonic fibroblasts (MEFs) to establish the cell death characteristics and the metabolic adaptive responses provoked by the mitochondrial electron transport chain (ETC) breakdown. Results: AIF deficiency destabilized mitochondrial ETC and provoked supercomplex disorganization, mitochondrial transmembrane potential loss, and high generation of mitochondrial reactive oxygen species (ROS). AIF Conclusions: In a single knockout model and at 3 different levels (cell, embryo, and adult mice) we demonstrated that by controlling the mitochondrial OXPHOS/metabolism, AIF is a key factor regulating cell differentiation and fate. Additionally, by providing new insights into the pathological consequences of mitochondrial OXPHOS dysfunction, our new findings pave the way for novel pharmacological strategies.
MeSH term(s)	Animals ; Apoptosis/physiology ; Apoptosis Inducing Factor/genetics ; Apoptosis Inducing Factor/metabolism ; Caspases/metabolism ; Cell Respiration ; Female ; Fibroblasts/metabolism ; Genetic Engineering/methods ; Glycolysis/genetics ; Hydrocephalus/metabolism ; Male ; Membrane Potential, Mitochondrial/genetics ; Membrane Potential, Mitochondrial/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains/genetics ; Mitochondria/metabolism ; Models, Animal ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism
Chemical Substances	Apoptosis Inducing Factor ; AIFM1 protein, mouse ; Reactive Oxygen Species ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2020-05-30
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2020.101027
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Article ; Online: 1st EFIS-EJI intensive course in clinical immunology: towards a new era in immunology.

Cabon, Lauriane / Chatterjee, Saradiya / Delavallée, Laure / Le Quintrec, Moglie / Maître, Mikaël / Roumenina, Lubka T

European journal of immunology

2011 Volume 41, Issue 2, Page(s) 268–269

MeSH term(s)	Allergy and Immunology/education ; Autoimmune Diseases/immunology ; Autoimmunity/immunology ; Biomarkers ; Curriculum ; Education, Medical ; Humans ; Immune Tolerance/immunology ; Immunity/immunology ; Immunotherapy/methods ; Immunotherapy/trends ; Inflammation/immunology ; Paris ; Vaccines/immunology
Chemical Substances	Biomarkers ; Vaccines
Language	English
Publishing date	2011-02
Publishing country	Germany
Document type	News
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201190002
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: AIF-mediated caspase-independent necroptosis: a new chance for targeted therapeutics.

Delavallée, Laure / Cabon, Lauriane / Galán-Malo, Patricia / Lorenzo, Hans K / Susin, Santos A

IUBMB life

2011 Volume 63, Issue 4, Page(s) 221–232

Abstract: Cell death has been initially divided into apoptosis, in which the cell plays an active role, and necrosis, which is considered a passive cell death program. Intense research performed in the last decades has concluded that "programmed" cell death (PCD) ... ...

Abstract	Cell death has been initially divided into apoptosis, in which the cell plays an active role, and necrosis, which is considered a passive cell death program. Intense research performed in the last decades has concluded that "programmed" cell death (PCD) is a more complex physiological process than initially thought. Indeed, although in most cases the PCD process is achieved via a family of Cys proteases known as caspases, an important number of regulated PCD pathways do not involve this family of proteases. As a consequence, active forms of PCD are initially referred to as caspase-dependent and caspase-independent. More recent data has revealed that there are also active caspase-independent necrotic pathways defined as necroptosis (programmed necrosis). The existence of necroptotic forms of death was corroborated by the discovery of key executioners such as the kinase RIP1 or the mitochondrial protein apoptosis-inducing factor (AIF). AIF is a Janus protein with a redox activity in the mitochondria and a pro-apoptotic function in the nucleus. We have recently described a particular form of AIF-mediated caspase-independent necroptosis that also implicates other molecules such as PARP-1, calpains, Bax, Bcl-2, histone H2AX, and cyclophilin A. From a therapeutic point of view, the unraveling of this new form of PCD poses a question: is it possible to modulate this necroptotic pathway independently of the classical apoptotic paths? Because the answer is yes, a wider understanding of AIF-mediated necroptosis could theoretically pave the way for the development of new drugs that modulate PCD. To this end, we present here an overview of the current knowledge of AIF and AIF-mediated necroptosis. We also summarize the state of the art in some of the most interesting therapeutic strategies that could target AIF or the AIF-mediated necroptotic pathway.
MeSH term(s)	Amino Acid Sequence ; Animals ; Apoptosis Inducing Factor/genetics ; Apoptosis Inducing Factor/metabolism ; Caspases/metabolism ; Cell Death/drug effects ; Cell Death/physiology ; Conserved Sequence ; Humans ; Mitochondria/metabolism ; Molecular Targeted Therapy
Chemical Substances	Apoptosis Inducing Factor ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2011-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1492141-8
ISSN	1521-6551 ; 1521-6543
ISSN (online)	1521-6551
ISSN	1521-6543
DOI	10.1002/iub.432
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Zs.A 1611: Show issues

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Article ; Online: AIF loss deregulates hematopoiesis and reveals different adaptive metabolic responses in bone marrow cells and thymocytes.

Cabon, Lauriane / Bertaux, Audrey / Brunelle-Navas, Marie-Noëlle / Nemazanyy, Ivan / Scourzic, Laurianne / Delavallée, Laure / Vela, Laura / Baritaud, Mathieu / Bouchet, Sandrine / Lopez, Cécile / Quang Van, Vu / Garbin, Kevin / Chateau, Danielle / Gilard, Françoise / Sarfati, Marika / Mercher, Thomas / Bernard, Olivier A / Susin, Santos A

Cell death and differentiation

2018 Volume 25, Issue 5, Page(s) 983–1001

Abstract: Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated ... ...

Abstract	Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF
MeSH term(s)	Animals ; Apoptosis Inducing Factor/deficiency ; B-Lymphocytes/cytology ; B-Lymphocytes/metabolism ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Mice ; Mice, Knockout ; Mitochondria/genetics ; Mitochondria/metabolism ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism ; Thymocytes/cytology ; Thymocytes/metabolism
Chemical Substances	Apoptosis Inducing Factor ; AIFM1 protein, mouse ; Reactive Oxygen Species
Language	English
Publishing date	2018-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-017-0035-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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