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  • 1
    Publication Date: 2008-02-29
    Description: Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670399/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670399/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mizushima, Noboru -- Levine, Beth -- Cuervo, Ana Maria -- Klionsky, Daniel J -- R01 AG021904/AG/NIA NIH HHS/ -- R01 AG021904-06/AG/NIA NIH HHS/ -- R03 AG019834/AG/NIA NIH HHS/ -- R03 AG019834-02/AG/NIA NIH HHS/ -- R21 AG025355/AG/NIA NIH HHS/ -- R21 AG025355-02/AG/NIA NIH HHS/ -- England -- Nature. 2008 Feb 28;451(7182):1069-75. doi: 10.1038/nature06639.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305538" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Autophagy/immunology/*physiology ; Cell Death ; Cell Survival ; Humans ; Immunity, Innate/immunology ; Neoplasms/pathology ; Neurodegenerative Diseases/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-04-03
    Description: The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676208/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Rajat -- Kaushik, Susmita -- Wang, Yongjun -- Xiang, Youqing -- Novak, Inna -- Komatsu, Masaaki -- Tanaka, Keiji -- Cuervo, Ana Maria -- Czaja, Mark J -- K01 DK087776/DK/NIDDK NIH HHS/ -- P01 AG031782/AG/NIA NIH HHS/ -- P01 AG031782-01A1/AG/NIA NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 AG021904/AG/NIA NIH HHS/ -- R01 AG021904-07/AG/NIA NIH HHS/ -- R01 DK061498/DK/NIDDK NIH HHS/ -- R01 DK061498-05/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1131-5. doi: 10.1038/nature07976. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339967" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/drug effects/*physiology ; Cell Line ; Cholesterol/metabolism ; Dietary Fats/pharmacology ; Fatty Acids/*metabolism ; Food Deprivation ; Hepatocytes/cytology/drug effects/metabolism ; *Lipid Metabolism/drug effects ; Lipolysis/drug effects ; Liver/cytology/drug effects/metabolism ; Lysosomes/metabolism ; Mice ; Microtubule-Associated Proteins/deficiency/genetics ; Oxidation-Reduction ; Phagosomes/metabolism ; Rats ; Triglycerides/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-06-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuervo, Ana Maria -- New York, N.Y. -- Science. 2011 Jun 17;332(6036):1392-3. doi: 10.1126/science.1208607.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ana-maria.cuervo@einstein.yu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21680833" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; *Autophagy ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism ; Cell Nucleus/metabolism ; Cytosol/metabolism ; Humans ; Lysosomes/*metabolism ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Phagosomes/metabolism ; Phosphorylation ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2004-08-31
    Description: Aberrant alpha-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type alpha-synuclein is normally degraded. We found that wild-type alpha-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway. The pathogenic A53T and A30P alpha-synuclein mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates. These findings may underlie the toxic gain-of-function by the mutants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuervo, Ana Maria -- Stefanis, Leonidas -- Fredenburg, Ross -- Lansbury, Peter T -- Sulzer, David -- AG021904/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2004 Aug 27;305(5688):1292-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. amcuervo@aecom.yu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15333840" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Antigens, CD/metabolism ; *Autophagy ; Cells, Cultured ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism/pharmacology ; Half-Life ; Intracellular Membranes/metabolism ; Lysosome-Associated Membrane Glycoproteins ; Lysosomes/*metabolism ; Male ; Mice ; Molecular Chaperones/*metabolism ; Mutation ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Neurons/metabolism ; PC12 Cells ; Protein Binding ; Protein Transport ; Rats ; Rats, Wistar ; Synucleins ; alpha-Synuclein
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-10-04
    Description: Nutrient deprivation is a stimulus shared by both autophagy and the formation of primary cilia. The recently discovered role of primary cilia in nutrient sensing and signalling motivated us to explore the possible functional interactions between this signalling hub and autophagy. Here we show that part of the molecular machinery involved in ciliogenesis also participates in the early steps of the autophagic process. Signalling from the cilia, such as that from the Hedgehog pathway, induces autophagy by acting directly on essential autophagy-related proteins strategically located in the base of the cilium by ciliary trafficking proteins. Whereas abrogation of ciliogenesis partially inhibits autophagy, blockage of autophagy enhances primary cilia growth and cilia-associated signalling during normal nutritional conditions. We propose that basal autophagy regulates ciliary growth through the degradation of proteins required for intraflagellar transport. Compromised ability to activate the autophagic response may underlie some common ciliopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896125/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896125/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pampliega, Olatz -- Orhon, Idil -- Patel, Bindi -- Sridhar, Sunandini -- Diaz-Carretero, Antonio -- Beau, Isabelle -- Codogno, Patrice -- Satir, Birgit H -- Satir, Peter -- Cuervo, Ana Maria -- AG031782/AG/NIA NIH HHS/ -- AG038072/AG/NIA NIH HHS/ -- DK098408/DK/NIDDK NIH HHS/ -- P01 AG031782/AG/NIA NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 DK098408/DK/NIDDK NIH HHS/ -- R37 AG021904/AG/NIA NIH HHS/ -- England -- Nature. 2013 Oct 10;502(7470):194-200. doi: 10.1038/nature12639. Epub 2013 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24089209" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/genetics/*physiology ; Carrier Proteins/genetics/metabolism ; Cell Line ; Cilia/metabolism/*physiology ; Hedgehog Proteins/metabolism ; Mice ; Protein Transport ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-09-12
    Description: Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance. In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation. An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape. Landscape change is not a necessity for speciation in this model. Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Brian Tilston -- McCormack, John E -- Cuervo, Andres M -- Hickerson, Michael J -- Aleixo, Alexandre -- Cadena, Carlos Daniel -- Perez-Eman, Jorge -- Burney, Curtis W -- Xie, Xiaoou -- Harvey, Michael G -- Faircloth, Brant C -- Glenn, Travis C -- Derryberry, Elizabeth P -- Prejean, Jesse -- Fields, Samantha -- Brumfield, Robb T -- England -- Nature. 2014 Nov 20;515(7527):406-9. doi: 10.1038/nature13687. Epub 2014 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Ornithology, American Museum of Natural History, New York, New York 10024, USA [3]. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Biology Department, City College of New York, New York, New York 10031, USA [2] Division of Invertebrate Zoology, American Museum of Natural History, New York, New York 10024, USA. ; Coordenacao de Zoologia, Museu Paraense Emilio Goeldi, Caixa Postal 399, CEP 66040-170, Belem, Brazil. ; Laboratorio de Biologia Evolutiva de Vertebrados, Departamento de Ciencias Biologicas, Universidad de los Andes, Bogota, Colombia. ; 1] Instituto de Zoologia y Ecologia Tropical, Universidad Central de Venezuela, Av. Los Ilustres, Los Chaguaramos, Apartado Postal 47058, Caracas 1041-A, Venezuela [2] Coleccion Ornitologica Phelps, Apartado 2009, Caracas 1010-A, Venezuela. ; Biology Department, City College of New York, New York, New York 10031, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. ; 1] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209666" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Birds/*classification/*genetics ; *Genetic Speciation ; Models, Biological ; Molecular Sequence Data ; Panama ; *Phylogeny ; *Rainforest ; Rivers ; South America ; *Tropical Climate
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-07-26
    Description: Multiple pathways of protein degradation operate within cells. A selective protein import pathway exists for the uptake and degradation of particular cytosolic proteins by lysosomes. Here, the lysosomal membrane glycoprotein LGP96 was identified as a receptor for the selective import and degradation of proteins within lysosomes. Specific substrates of this proteolytic pathway bound to the cytosolic tail of a 96-kilodalton lysosomal membrane protein in two different binding assays. Overexpression of human LGP96 in Chinese hamster ovary cells increased the activity of the selective lysosomal proteolytic pathway in vivo and in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuervo, A M -- Dice, J F -- AG06116/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):501-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662539" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD/chemistry/*metabolism ; CHO Cells ; Cricetinae ; Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism ; HSC70 Heat-Shock Proteins ; *HSP70 Heat-Shock Proteins ; Heat-Shock Proteins/metabolism ; Humans ; Intracellular Membranes/metabolism ; Lysosomal-Associated Membrane Protein 2 ; Lysosome-Associated Membrane Glycoproteins ; Lysosomes/*metabolism ; Membrane Glycoproteins/chemistry/*metabolism ; Molecular Sequence Data ; Proteins/*metabolism ; Rats ; Ribonuclease, Pancreatic/*metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2012-02-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2006-04-03
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2012-04-25
    Description: Mutations leading to expansion of a poly-glutamine track in Huntingtin (Htt) cause Huntington's disease (HD). Signs of endoplasmic reticulum (ER) stress have been recently reported in animal models of HD, associated with the activation of the unfolded protein response (UPR). Here we have investigated the functional contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice. XBP1-deficient mice were more resistant to developing disease features, associated with improved neuronal survival and motor performance, and a drastic decrease in mHtt levels. The protective effects of XBP1 deficiency were associated with enhanced macroautophagy in both cellular and animal models of HD. In contrast, ATF4 deficiency did not alter mHtt levels. Although, XBP1 mRNA splicing was observed in the striatum of HD transgenic brains, no changes in the levels of classical ER stress markers were detected in symptomatic animals. At the mechanistic level, we observed that XBP1 deficiency led to augmented expression of Forkhead box O1 (FoxO1), a key transcription factor regulating autophagy in neurons. In agreement with this finding, ectopic expression of FoxO1 enhanced autophagy and mHtt clearance in vitro . Our results provide strong evidence supporting an involvement of XBP1 in HD pathogenesis probably due to an ER stress-independent mechanism involving the control of FoxO1 and autophagy levels.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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