المؤلفون: Marie-Lise Lacombe, Frederic Lamarche, Olivier De Wever, Teresita Padilla-Benavides, Alyssa Carlson, Imran Khan, Anda Huna, Sophie Vacher, Claire Calmel, Céline Desbourdes, Cécile Cottet-Rousselle, Isabelle Hininger-Favier, Stéphane Attia, Béatrice Nawrocki-Raby, Joël Raingeaud, Christelle Machon, Jérôme Guitton, Morgane Le Gall, Guilhem Clary, Cedric Broussard, Philippe Chafey, Patrice Thérond, David Bernard, Eric Fontaine, Malgorzata Tokarska-Schlattner, Patricia Steeg, Ivan Bièche, Uwe Schlattner, Mathieu Boissan

المصدر: BMC Biology, Vol 19, Iss 1, Pp 1-29 (2021)

مصطلحات موضوعية: Mitochondrial dynamics, Invasion, Metastasis, Nucleoside diphosphate kinase, NME4, Metabolic reprogramming, Biology (General), QH301-705.5

الوصف: Abstract Background Mitochondrial nucleoside diphosphate kinase (NDPK-D, NME4, NM23-H4) is a multifunctional enzyme mainly localized in the intermembrane space, bound to the inner membrane. Results We constructed loss-of-function mutants of NDPK-D, lacking either NDP kinase activity or membrane interaction and expressed mutants or wild-type protein in cancer cells. In a complementary approach, we performed depletion of NDPK-D by RNA interference. Both loss-of-function mutations and NDPK-D depletion promoted epithelial-mesenchymal transition and increased migratory and invasive potential. Immunocompromised mice developed more metastases when injected with cells expressing mutant NDPK-D as compared to wild-type. This metastatic reprogramming is a consequence of mitochondrial alterations, including fragmentation and loss of mitochondria, a metabolic switch from respiration to glycolysis, increased ROS generation, and further metabolic changes in mitochondria, all of which can trigger pro-metastatic protein expression and signaling cascades. In human cancer, NME4 expression is negatively associated with markers of epithelial-mesenchymal transition and tumor aggressiveness and a good prognosis factor for beneficial clinical outcome. Conclusions These data demonstrate NME4 as a novel metastasis suppressor gene, the first localizing to mitochondria, pointing to a role of mitochondria in metastatic dissemination.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1741-7007Test

الوصول الحر: https://doaj.org/article/64c3e3bcb5024675ac11f551606b20d8Test

المؤلفون: Jonathan Gaucher, Guillaume Vial, Emilie Montellier, Maëlle Guellerin, Sophie Bouyon, Emeline Lemarie, Véronique Pelloux, Anne Bertrand, Karin Pernet-Gallay, Frederic Lamarche, Anne-Laure Borel, Claire Arnaud, Elise Belaidi, Karine Clément, Diane Godin Ribuot, Judith Aron-Wisnewsky, Jean-Louis Pépin

المصدر: Frontiers in Medicine, Vol 9 (2022)

مصطلحات موضوعية: sleep apnea, intermittent hypoxia (IH), liver, transcriptome, mitochondria, Nuclear Respiratory Factor (NRF), Medicine (General), R5-920

الوصف: Sleep Apnea Syndrome (SAS) is one of the most common chronic diseases, affecting nearly one billion people worldwide. The repetitive occurrence of abnormal respiratory events generates cyclical desaturation-reoxygenation sequences known as intermittent hypoxia (IH). Among SAS metabolic sequelae, it has been established by experimental and clinical studies that SAS is an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The principal goal of this study was to decrypt the molecular mechanisms at the onset of IH-mediated liver injury. To address this question, we used a unique mouse model of SAS exposed to IH, employed unbiased high-throughput transcriptomics and computed network analysis. This led us to examine hepatic mitochondrial ultrastructure and function using electron microscopy, high-resolution respirometry and flux analysis in isolated mitochondria. Transcriptomics and network analysis revealed that IH reprograms Nuclear Respiratory Factor- (NRF-) dependent gene expression and showed that mitochondria play a central role. We thus demonstrated that IH boosts the oxidative capacity from fatty acids of liver mitochondria. Lastly, the unbalance between oxidative stress and antioxidant defense is tied to an increase in hepatic ROS production and DNA damage during IH. We provide a comprehensive analysis of liver metabolism during IH and reveal the key role of the mitochondria at the origin of development of liver disease. These findings contribute to the understanding of the mechanisms underlying NAFLD development and progression during SAS and provide a rationale for novel therapeutic targets and biomarker discovery.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2022.829979/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/2fb81fb83bf14c2cae33002c3c42c0ebTest

المؤلفون: Anaïs Alves, Frédéric Lamarche, Rémy Lefebvre, Eva Drevet Mulard, Arthur Bassot, Stéphanie Chanon, Emmanuelle Loizon, Claudie Pinteur, Aline Maria Nunes de Lira Gomes Bloise, Murielle Godet, Gilles J. P. Rautureau, Baptiste Panthu, Béatrice Morio

المصدر: Nutrients; Volume 15; Issue 1; Pages: 96

مصطلحات موضوعية: dietary supplement, amino acid metabolism, obesity-related metabolic disorders, insulin resistance, mitochondria

جغرافية الموضوع: agris

الوصف: Interactions between mitochondria and the endoplasmic reticulum, known as MAMs, are altered in the liver in obesity, which contributes to disruption of the insulin signaling pathway. In addition, the plasma level of glycine is decreased in obesity, and the decrease is strongly correlated with the severity of insulin resistance. Certain nutrients have been shown to regulate MAMs; therefore, we tested whether glycine supplementation could reduce insulin resistance in the liver by promoting MAM integrity. Glycine (5 mM) supported MAM integrity and insulin response in primary rat hepatocytes cultured under control and lipotoxic (palmitate 500 µM) conditions for 18 h. In contrast, in C57 BL/6 JOlaHsd mice (male, 6 weeks old) fed a high-fat, high-sucrose diet (HFHS) for 16 weeks, glycine supplementation (300 mg/kg) in drinking water during the last 6 weeks (HFHS-Gly) did not reverse the deleterious impact of HFHS-feeding on liver MAM integrity. In addition, glycine supplementation worsened fasting glycemia and glycemic response to intraperitoneal pyruvate injection compared to HFHS. The adverse impact of glycine supplementation on hepatic gluconeogenesis was further supported by the higher oxaloacetate/acetyl-CoA ratio in the liver in HFHS-Gly compared to HFHS. Although glycine improves MAM integrity and insulin signaling in the hepatocyte in vitro, no beneficial effect was found on the overall metabolic profile of HFHS-Gly-fed mice.

وصف الملف: application/pdf

العلاقة: Proteins and Amino Acids; https://dx.doi.org/10.3390/nu15010096Test

الإتاحة: https://doi.org/10.3390/nu15010096Test

المؤلفون: Sophie Moulin, Amandine Thomas, Stefan Wagner, Michael Arzt, Hervé Dubouchaud, Frédéric Lamarche, Sophie Bouyon, Guillaume Vial, Diane Godin-Ribuot, Jean-Louis Pépin, Claire Arnaud, Elise Belaidi

المصدر: Antioxidants; Volume 11; Issue 8; Pages: 1462

مصطلحات موضوعية: sleep disordered breathing, intermittent hypoxia, hypoxia inducible factor-1, mitochondria associated-ER membrane, cardiomyocyte death

جغرافية الموضوع: agris

الوصف: Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation. Methods: Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α+/− mice were exposed to normoxia (N) or IH (21–5% O2, 60 cycles/h, 8 h/day) for 21 days. Expressions of HIF-1α, Grp78 and CHOP, and apoptosis, were measured by Western blot and immunochemistry. In isolated cardiomyocytes, we examined structural integrity of MAM by proximity ligation assay and their function by measuring ER-to-mitochondria Ca2+ transfer by confocal microscopy. Finally, we measured mitochondrial respiration using oxygraphy and calcium retention capacity (CRC) by spectrofluorometry. MAM structure was also investigated in H9C2 cells incubated with 1 mM CoCl2, a potent HIF-1α inducer. Results: In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca2+ homeostasis, mitochondrial respiration and CRC. Importantly, IH had no effect in HIF-1α+/− mice. Similar to what observed under IH, HIF-1α overexpression was associated with MAM alteration in H9C2. Conclusion: IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.

وصف الملف: application/pdf

العلاقة: Health Outcomes of Antioxidants and Oxidative Stress; https://dx.doi.org/10.3390/antiox11081462Test

الإتاحة: https://doi.org/10.3390/antiox11081462Test

المؤلفون: Malgorzata Tokarska-Schlattner, Laurence Kay, Pascale Perret, Raffaella Isola, Stéphane Attia, Frédéric Lamarche, Cindy Tellier, Cécile Cottet-Rousselle, Amjad Uneisi, Isabelle Hininger-Favier, Marc Foretz, Hervé Dubouchaud, Catherine Ghezzi, Christian Zuppinger, Benoit Viollet and Uwe Schlattner

المساهمون: Tokarska-Schlattner, Malgorzata, Kay, Laurence, Perret, Pascale, Isola, Raffaella, Attia, Stéphane, Lamarche, Frédéric, Tellier, Cindy, Cottet-Rousselle, Cécile, Uneisi, Amjad, Hininger-Favier, Isabelle, Foretz, Marc, Dubouchaud, Hervé, Ghezzi, Catherine, Zuppinger, Christian, Viollet and Uwe Schlattner, Benoit

مصطلحات موضوعية: AMP-activated protein kinase, AMPK, Heart, Conditional inducible KO, Energetic, Exercise, Mitochondria

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34733845; info:eu-repo/semantics/altIdentifier/wos/WOS:000715709800001; volume:9; firstpage:1; lastpage:18; numberofpages:18; journal:FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY; http://hdl.handle.net/11584/320267Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85118334310

الإتاحة: https://doi.org/10.3389/fcell.2021.731015Test
http://hdl.handle.net/11584/320267Test

المؤلفون: Marie-Lise Lacombe (11593719), Frederic Lamarche (2001721), Olivier De Wever (6885914), Teresita Padilla-Benavides (2632399), Alyssa Carlson (11593722), Imran Khan (109715), Anda Huna (841989), Sophie Vacher (233965), Claire Calmel (421263), Céline Desbourdes (11593725), Cécile Cottet-Rousselle (363145), Isabelle Hininger-Favier (11574988), Stéphane Attia (11574979), Béatrice Nawrocki-Raby (58024), Joël Raingeaud (261681), Christelle Machon (816152), Jérôme Guitton (816154), Morgane Le Gall (11593728), Guilhem Clary (11593731), Cedric Broussard (11593734), Philippe Chafey (210556), Patrice Thérond (372067), David Bernard (242005), Eric Fontaine (363147), Malgorzata Tokarska-Schlattner (311096), Patricia Steeg (6374513), Ivan Bièche (3492), Uwe Schlattner (18191), Mathieu Boissan (8262003)

مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Developmental Biology, Cancer, Hematology, Infectious Diseases, Computational Biology, Mitochondrial dynamics, Invasion, Metastasis, Nucleoside diphosphate kinase, NME4, Metabolic reprogramming, Prognosis biomarker, Retrograde signaling

الوصف: Additional file 10: Table S1. Differently expressed proteins in HeLa clones expressing the mutant and the wild type NDPK-D. The full protein names are from the UniProt database. Accession number are from UniProt (Acc._HUMAN) and SwissProt databases. The one-way analysis of variance (ANOVA) test, followed by a Tukey’s multiple comparison test, was used to determine protein spots significantly different between analyses. p-values were calculated across pairwise comparisons (clones KD vs WT, BD vs WT and CTR vs WT) and considered significant when < 0.05. Proteins were ordered following the fold changes in the KD vs WT comparison. * Two identifications for the same spot. Bold values, fold change statistically significant (p< 0.05) and ≥1.3. Italic values, fold change not statistically valid (p > 0.05) or ≤1.3. § Proteins reported to present a mitochondrial localization (UniProt annotation) are indicated by M.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_10_of_The_mitochondrially-localized_nucleoside_diphosphate_kinase_D_NME4_is_a_novel_metastasis_suppressor/16851063Test

الإتاحة: https://doi.org/10.6084/m9.figshare.16851063.v1Test

المؤلفون: Marie-Lise Lacombe (11593719), Frederic Lamarche (2001721), Olivier De Wever (6885914), Teresita Padilla-Benavides (2632399), Alyssa Carlson (11593722), Imran Khan (109715), Anda Huna (841989), Sophie Vacher (233965), Claire Calmel (421263), Céline Desbourdes (11593725), Cécile Cottet-Rousselle (363145), Isabelle Hininger-Favier (11574988), Stéphane Attia (11574979), Béatrice Nawrocki-Raby (58024), Joël Raingeaud (261681), Christelle Machon (816152), Jérôme Guitton (816154), Morgane Le Gall (11593728), Guilhem Clary (11593731), Cedric Broussard (11593734), Philippe Chafey (210556), Patrice Thérond (372067), David Bernard (242005), Eric Fontaine (363147), Malgorzata Tokarska-Schlattner (311096), Patricia Steeg (6374513), Ivan Bièche (3492), Uwe Schlattner (18191), Mathieu Boissan (8262003)

مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Developmental Biology, Cancer, Hematology, Infectious Diseases, Computational Biology, Mitochondrial dynamics, Invasion, Metastasis, Nucleoside diphosphate kinase, NME4, Metabolic reprogramming, Prognosis biomarker, Retrograde signaling

الوصف: Additional file 20: Table S3. Characteristics of the 526 human breast tumor cohort.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_20_of_The_mitochondrially-localized_nucleoside_diphosphate_kinase_D_NME4_is_a_novel_metastasis_suppressor/16851105Test

الإتاحة: https://doi.org/10.6084/m9.figshare.16851105.v1Test

المؤلفون: Bastien Proust (11721510), Martina Radić (11721513), Nikolina Škrobot Vidaček (11721516), Cécile Cottet (11721519), Stéphane Attia (11574979), Frédéric Lamarche (6456203), Lucija Ačkar (11721522), Vlatka Godinić Mikulčić (11721525), Malgorzata Tokarska-Schlattner (311096), Helena Ćetković (145489), Uwe Schlattner (18191), Maja Herak Bosnar (11721528)

مصطلحات موضوعية: Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Cancer, Infectious Diseases, NDP kinase, NME, nm23, Mitochondria, RCC1L, WBSCR16

الوصف: Additional file 1: Table. S1 Plasmids used in the study.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_NME6_is_a_phosphotransfer-inactive_monomeric_NME_NDPK_family_member_and_functions_in_complexes_at_the_interface_of_mitochondrial_inner_membrane_and_matrix/17037615Test

الإتاحة: https://doi.org/10.6084/m9.figshare.17037615.v1Test

المؤلفون: Guillaume Vial, Frédéric Lamarche, Cécile Cottet‐Rousselle, Sophie Hallakou‐Bozec, Anne‐Laure Borel, Eric Fontaine

المصدر: Endocrinology, Diabetes & Metabolism, Vol 4, Iss 2, Pp n/a-n/a (2021)

مصطلحات موضوعية: complex I, imeglimin, metformin, mitochondria, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Aims To understand the mechanism by which imeglimin (a new oral hypoglycemic agent whose phase 3 development program in Japan has now been completed) decreases hepatic glucose production. Materials and methods We compared the effect of imeglimin and metformin on glucose production, ATP/ADP ratio, oxygen consumption rate, mitochondrial redox potential and membrane potential in primary rat hepatocytes. Results We found that both imeglimin and metformin dose‐dependently decreased glucose production and the ATP/ADP ratio. Moreover, they both increased mitochondrial redox potential (assessed by mitochondrial NAD(P)H fluorescence) and decreased membrane potential (assessed by TMRM fluorescence). However, contrary to metformin, which inhibits mitochondrial Complex I, imeglimin did not decrease the oxygen consumption rate in intact cells. By measuring the oxygen consumption of in situ respiratory chain as a function of the concentration of NADH, we observed that imeglimin decreased the affinity of NADH for the respiratory chain but did not affect its Vmax (ie competitive inhibition) whereas metformin decreased both the Vmax and the affinity (ie uncompetitive inhibition). Conclusions We conclude that imeglimin induces a kinetic constraint on the respiratory chain that does not affect its maximal activity. This kinetic constraint is offset by a decrease in the mitochondrial membrane potential, which induces a thermodynamic constraint on the ATPase responsible for a decrease in the ATP/ADP ratio.

العلاقة: https://doi.org/10.1002/edm2.211Test; https://doaj.org/toc/2398-9238Test; https://doaj.org/article/d9bf9e70fc6e487d922d50307e720565Test

الإتاحة: https://doi.org/10.1002/edm2.211Test
https://doaj.org/article/d9bf9e70fc6e487d922d50307e720565Test

المؤلفون: Bastien Proust, Martina Radić, Nikolina Škrobot Vidaček, Cécile Cottet, Stéphane Attia, Frédéric Lamarche, Lucija Ačkar, Vlatka Godinić Mikulčić, Malgorzata Tokarska-Schlattner, Helena Ćetković, Uwe Schlattner, Maja Herak Bosnar

المصدر: Cell & Bioscience, Vol 11, Iss 1, Pp 1-23 (2021)

مصطلحات موضوعية: NDP kinase, NME, nm23, Mitochondria, RCC1L, WBSCR16, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436

الوصف: Background NME6 is a member of the nucleoside diphosphate kinase (NDPK/NME/Nm23) family which has key roles in nucleotide homeostasis, signal transduction, membrane remodeling and metastasis suppression. The well-studied NME1-NME4 proteins are hexameric and catalyze, via a phospho-histidine intermediate, the transfer of the terminal phosphate from (d)NTPs to (d)NDPs (NDP kinase) or proteins (protein histidine kinase). For the NME6, a gene/protein that emerged early in eukaryotic evolution, only scarce and partially inconsistent data are available. Here we aim to clarify and extend our knowledge on the human NME6. Results We show that NME6 is mostly expressed as a 186 amino acid protein, but that a second albeit much less abundant isoform exists. The recombinant NME6 remains monomeric, and does not assemble into homo-oligomers or hetero-oligomers with NME1-NME4. Consequently, NME6 is unable to catalyze phosphotransfer: it does not generate the phospho-histidine intermediate, and no NDPK activity can be detected. In cells, we could resolve and extend existing contradictory reports by localizing NME6 within mitochondria, largely associated with the mitochondrial inner membrane and matrix space. Overexpressing NME6 reduces ADP-stimulated mitochondrial respiration and complex III abundance, thus linking NME6 to dysfunctional oxidative phosphorylation. However, it did not alter mitochondrial membrane potential, mass, or network characteristics. Our screen for NME6 protein partners revealed its association with NME4 and OPA1, but a direct interaction was observed only with RCC1L, a protein involved in mitochondrial ribosome assembly and mitochondrial translation, and identified as essential for oxidative phosphorylation. Conclusions NME6, RCC1L and mitoribosomes localize together at the inner membrane/matrix space where NME6, in concert with RCC1L, may be involved in regulation of the mitochondrial translation of essential oxidative phosphorylation subunits. Our findings suggest new functions for NME6, ...

العلاقة: https://doi.org/10.1186/s13578-021-00707-0Test; https://doaj.org/toc/2045-3701Test; https://doaj.org/article/6a3e0a4c508a420bb6a3fed81f79b808Test

الإتاحة: https://doi.org/10.1186/s13578-021-00707-0Test
https://doaj.org/article/6a3e0a4c508a420bb6a3fed81f79b808Test