The Experts below are selected from a list of 2532 Experts worldwide ranked by ideXlab platform

Mireia Nisosantano - One of the best experts on this subject based on the ideXlab platform.

  • unsaturated fatty acids induce non canonical autophagy
    The EMBO Journal, 2015
    Co-Authors: Mireia Nisosantano, Shoaib Ahmad Malik, Valentina Cianfanelli, Amena Benyounes, Rodrigo Troncoso, Maria Markaki, Jose Manuel Bravosan Pedro, Federico Pietrocola, Guillermo Marino, Valentina Sica
    Abstract:

    To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, BECN1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.

  • novel inducers of BECN1 independent autophagy cis unsaturated fatty acids
    Autophagy, 2015
    Co-Authors: Mireia Nisosantano, Lorenzo Galluzzi, Nektarios Tavernarakis, Jose Manuel Bravosan Pedro, Francesco Cecconi, Patrice Codogno, Maria Chiara Maiuri, Frank Madeo, Guido Kroemer
    Abstract:

    The induction of autophagy usually requires the activation of PIK3C3/VPS34 (phosphatidylinositol 3-kinase, catalytic subunit type 3) within a multiprotein complex that contains BECN1 (Beclin 1, autophagy related). PIK3C3 catalyzes the conversion of phosphatidylinositol into phosphatidylinositol 3-phosphate (PtdIns3P). PtdIns3P associates with growing phagophores, which recruit components of the autophagic machinery, including the lipidated form of MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3 β). Depletion of BECN1, PIK3C3 or some of their interactors suppresses the formation of MAP1LC3B+ phagophores or autophagosomes elicited by most physiological stimuli, including saturated fatty acids. We observed that cis-unsaturated fatty acids stimulate the generation of cytosolic puncta containing lipidated MAP1LC3B as well as the autophagic turnover of long-lived proteins in the absence of PtdIns3P accumulation. In line with this notion, cis-unsaturated fatty acids require neither BECN1 nor PIK3C3 to stimulate the autophagic flux. Such a BECN1-independent autophagic response is phylogenetically conserved, manifesting in yeast, nematodes, mice and human cells. Importantly, MAP1LC3B+ puncta elicited by cis-unsaturated fatty acids colocalize with Golgi apparatus markers. Moreover, the structural and functional collapse of the Golgi apparatus induced by brefeldin A inhibits cis-unsaturated fatty acid-triggered autophagy. It is tempting to speculate that the well-established health-promoting effects of cis-unsaturated fatty acids are linked to their unusual capacity to stimulate noncanonical, BECN1-independent autophagic responses.

Guido Kroemer - One of the best experts on this subject based on the ideXlab platform.

  • novel inducers of BECN1 independent autophagy cis unsaturated fatty acids
    Autophagy, 2015
    Co-Authors: Mireia Nisosantano, Lorenzo Galluzzi, Nektarios Tavernarakis, Jose Manuel Bravosan Pedro, Francesco Cecconi, Patrice Codogno, Maria Chiara Maiuri, Frank Madeo, Guido Kroemer
    Abstract:

    The induction of autophagy usually requires the activation of PIK3C3/VPS34 (phosphatidylinositol 3-kinase, catalytic subunit type 3) within a multiprotein complex that contains BECN1 (Beclin 1, autophagy related). PIK3C3 catalyzes the conversion of phosphatidylinositol into phosphatidylinositol 3-phosphate (PtdIns3P). PtdIns3P associates with growing phagophores, which recruit components of the autophagic machinery, including the lipidated form of MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3 β). Depletion of BECN1, PIK3C3 or some of their interactors suppresses the formation of MAP1LC3B+ phagophores or autophagosomes elicited by most physiological stimuli, including saturated fatty acids. We observed that cis-unsaturated fatty acids stimulate the generation of cytosolic puncta containing lipidated MAP1LC3B as well as the autophagic turnover of long-lived proteins in the absence of PtdIns3P accumulation. In line with this notion, cis-unsaturated fatty acids require neither BECN1 nor PIK3C3 to stimulate the autophagic flux. Such a BECN1-independent autophagic response is phylogenetically conserved, manifesting in yeast, nematodes, mice and human cells. Importantly, MAP1LC3B+ puncta elicited by cis-unsaturated fatty acids colocalize with Golgi apparatus markers. Moreover, the structural and functional collapse of the Golgi apparatus induced by brefeldin A inhibits cis-unsaturated fatty acid-triggered autophagy. It is tempting to speculate that the well-established health-promoting effects of cis-unsaturated fatty acids are linked to their unusual capacity to stimulate noncanonical, BECN1-independent autophagic responses.

  • bax and bak1 are dispensable for abt 737 induced dissociation of the bcl2 BECN1 complex and autophagy
    Autophagy, 2015
    Co-Authors: Jose Manuel Bravosan Pedro, Valentina Sica, Guido Kroemer, Maria Chiara Maiuri, Yongjie Wei, Zhongju Zou, Beth Levine
    Abstract:

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

  • pathogenic role of BECN1 beclin 1 in the development of amyotrophic lateral sclerosis
    Autophagy, 2014
    Co-Authors: Melissa Nassif, Guido Kroemer, Beth Levine, Vicente Valenzuela, Diego Rojasrivera, Rene L Vidal, Soledad Matus, Karen Castillo, Yerko Fuentealba, Claudio Hetz
    Abstract:

    Pharmacological activation of autophagy is becoming an attractive strategy to induce the selective degradation of aggregate-prone proteins. Recent evidence also suggests that autophagy impairment may underlie the pathogenesis of several neurodegenerative diseases. Mutations in the gene encoding SOD1 (superoxide disumutase 1) trigger familial amyotrophic lateral sclerosis (ALS), inducing its misfolding and aggregation and the progressive loss of motoneurons. It is still under debate whether autophagy has a protective or detrimental role in ALS. Here we evaluate the impact of BECN1/Beclin 1, an essential autophagy regulator, in ALS. BECN1 levels were upregulated in both cells and animals expressing mutant SOD1. To evaluate the impact of BECN1 to the pathogenesis of ALS in vivo, we generated mutant SOD1 transgenic mice heterozygous for BECN1. We observed an unexpected increase in life span of mutant SOD1 transgenic mice haploinsufficient for BECN1 compared with littermate control animals. These effects were accompanied by enhanced accumulation of SQSTM1/p62 and reduced levels of LC3-II, and an altered equilibrium between monomeric and oligomeric mutant SOD1 species in the spinal cord. At the molecular level, we detected an abnormal interaction of mutant SOD1 with the BECN1-BCL2L1 complex that may impact autophagy stimulation. Our data support a dual role of BECN1 in ALS and depict a complex scenario in terms of predicting the effects of manipulating autophagy in a disease context.

Chi-ming Liang - One of the best experts on this subject based on the ideXlab platform.

  • Recombinant protein rVP1 upregulates BECN1-independent autophagy, MAPK1/3 phosphorylation and MMP9 activity via WIPI1/WIPI2 to promote macrophage migration.
    Autophagy, 2013
    Co-Authors: Chiao-chun Liao, Shu-mei Liang, Chi-ming Liang
    Abstract:

    The monocyte/macrophage is critical for regulating immune and antitumor responses. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus induces apoptosis and inhibits migration/metastasis of cancer cells. Here, we explored the effects of rVP1 on macrophages. Our results showed that rVP1 increased LC3-related autophagosome formation via WIPI1 and WIPI2 in a BECN1-independent manner. rVP1 treatment increased macrophage migration that was attenuated by knockdown of ATG5, ATG7, WIPI1 or WIPI2 and was abolished when both WIPI1 and WIPI2 were depleted. Treatment of macrophages with rVP1 increased matrix metalloproteinase-9 (MMP9) activity and phosphorylated mitogen-activated protein kinase 1/3 (MAPK1/3), two major mediators of cell migration. Knockdown of WIPI1, WIPI2, ATG5 and ATG7 but not BECN1 attenuated the rVP1-mediated increase in MAPK1/3 phosphorylation and MMP9 activity. These results indicated that rVP1 upregulated autophagy, MAPK1/3 phosphorylation and MMP9 activity to promote macrophage migration, which was dependent on WIPI1, WIPI2, ATG5 and ATG7 but not BECN1.

  • recombinant protein rvp1 upregulates BECN1 independent autophagy mapk1 3 phosphorylation and mmp9 activity via wipi1 wipi2 to promote macrophage migration
    Autophagy, 2013
    Co-Authors: Chiao-chun Liao, Shu-mei Liang, Chi-ming Liang
    Abstract:

    The monocyte/macrophage is critical for regulating immune and antitumor responses. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus induces apoptosis and inhibits migration/metastasis of cancer cells. Here, we explored the effects of rVP1 on macrophages. Our results showed that rVP1 increased LC3-related autophagosome formation via WIPI1 and WIPI2 in a BECN1-independent manner. rVP1 treatment increased macrophage migration that was attenuated by knockdown of ATG5, ATG7, WIPI1 or WIPI2 and was abolished when both WIPI1 and WIPI2 were depleted. Treatment of macrophages with rVP1 increased matrix metalloproteinase-9 (MMP9) activity and phosphorylated mitogen-activated protein kinase 1/3 (MAPK1/3), two major mediators of cell migration. Knockdown of WIPI1, WIPI2, ATG5 and ATG7 but not BECN1 attenuated the rVP1-mediated increase in MAPK1/3 phosphorylation and MMP9 activity. These results indicated that rVP1 upregulated autophagy, MAPK1/3 phosphorylation and MMP9 activity to promote macrophage migration, which was dependent on WIPI1, WIPI2, ATG5 and ATG7 but not BECN1.

Jose Manuel Bravosan Pedro - One of the best experts on this subject based on the ideXlab platform.

  • unsaturated fatty acids induce non canonical autophagy
    The EMBO Journal, 2015
    Co-Authors: Mireia Nisosantano, Shoaib Ahmad Malik, Valentina Cianfanelli, Amena Benyounes, Rodrigo Troncoso, Maria Markaki, Jose Manuel Bravosan Pedro, Federico Pietrocola, Guillermo Marino, Valentina Sica
    Abstract:

    To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, BECN1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.

  • novel inducers of BECN1 independent autophagy cis unsaturated fatty acids
    Autophagy, 2015
    Co-Authors: Mireia Nisosantano, Lorenzo Galluzzi, Nektarios Tavernarakis, Jose Manuel Bravosan Pedro, Francesco Cecconi, Patrice Codogno, Maria Chiara Maiuri, Frank Madeo, Guido Kroemer
    Abstract:

    The induction of autophagy usually requires the activation of PIK3C3/VPS34 (phosphatidylinositol 3-kinase, catalytic subunit type 3) within a multiprotein complex that contains BECN1 (Beclin 1, autophagy related). PIK3C3 catalyzes the conversion of phosphatidylinositol into phosphatidylinositol 3-phosphate (PtdIns3P). PtdIns3P associates with growing phagophores, which recruit components of the autophagic machinery, including the lipidated form of MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3 β). Depletion of BECN1, PIK3C3 or some of their interactors suppresses the formation of MAP1LC3B+ phagophores or autophagosomes elicited by most physiological stimuli, including saturated fatty acids. We observed that cis-unsaturated fatty acids stimulate the generation of cytosolic puncta containing lipidated MAP1LC3B as well as the autophagic turnover of long-lived proteins in the absence of PtdIns3P accumulation. In line with this notion, cis-unsaturated fatty acids require neither BECN1 nor PIK3C3 to stimulate the autophagic flux. Such a BECN1-independent autophagic response is phylogenetically conserved, manifesting in yeast, nematodes, mice and human cells. Importantly, MAP1LC3B+ puncta elicited by cis-unsaturated fatty acids colocalize with Golgi apparatus markers. Moreover, the structural and functional collapse of the Golgi apparatus induced by brefeldin A inhibits cis-unsaturated fatty acid-triggered autophagy. It is tempting to speculate that the well-established health-promoting effects of cis-unsaturated fatty acids are linked to their unusual capacity to stimulate noncanonical, BECN1-independent autophagic responses.

  • bax and bak1 are dispensable for abt 737 induced dissociation of the bcl2 BECN1 complex and autophagy
    Autophagy, 2015
    Co-Authors: Jose Manuel Bravosan Pedro, Valentina Sica, Guido Kroemer, Maria Chiara Maiuri, Yongjie Wei, Zhongju Zou, Beth Levine
    Abstract:

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

Valentina Sica - One of the best experts on this subject based on the ideXlab platform.

  • unsaturated fatty acids induce non canonical autophagy
    The EMBO Journal, 2015
    Co-Authors: Mireia Nisosantano, Shoaib Ahmad Malik, Valentina Cianfanelli, Amena Benyounes, Rodrigo Troncoso, Maria Markaki, Jose Manuel Bravosan Pedro, Federico Pietrocola, Guillermo Marino, Valentina Sica
    Abstract:

    To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, BECN1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.

  • bax and bak1 are dispensable for abt 737 induced dissociation of the bcl2 BECN1 complex and autophagy
    Autophagy, 2015
    Co-Authors: Jose Manuel Bravosan Pedro, Valentina Sica, Guido Kroemer, Maria Chiara Maiuri, Yongjie Wei, Zhongju Zou, Beth Levine
    Abstract:

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.