Functional Consequences of Impaired Autophagy in Aging

Summary

Principal Investigator: ANA M CUERVO
Abstract: This is a new Program Project to investigate the role that age-related changes in autophagy play in the functional alterations and inefficient response to immunological challenges and to stress of old organisms. Four Projects involving 4 faculty members from 3 academic departments are proposed. These projects will share ideas, techniques and experimental models. Completion of most specific aims requires the participation of members from several of the projects. Degradation of intracellular components in lysosomes, or autophagy, is essential for cellular homeostasis, as an energy source when nutrients are sparse and in response to stress. The activity of the two best characterized types of autophagy, macroautophagy and chaperone-mediated autophagy, is altered in old organisms. We hypothesize that this impairment in autophagy could be behind the functional deterioration and the inability to respond to immunological challenges and to stress in old organism. To test this hypothesis we will: 1) characterize the involvement of different autophagic pathways in liver (Project 1 and 4), brain (P1) and the immune system (P2 and 3), under basal or stress conditions;2) analyze the changes with age in the autophagic system in these organs (P1-4);and 3) determine the contribution of these changes to the metabolic syndrome of aging (P4), the gradual deterioration of cognitive function (P1) and to the failure with age of two essential immune functions, antigen processing and presentation (P2) and T helper cell activation and tolerance (P3). These studies will require the synergistic cooperation of groups with expertise in autophagy, dendritic cell function, T cell biology, steatotic liver disease, lipid metabolism and oxidative cellular injury. This Program includes three Cores: the Administrative Core (Core A) provides the necessary secretarial and bookkeeping functions;the Analytical Imaging Core (Core B) provides state-of-the-art microscopy and imaging services, and the Aging and Transgenic Animal Core (Core C) provides maintenance, breeding and genotyping of the transgenic and aging mouse colonies required for this project. All four Projects are concerned with interrelated areas of cellular metabolism, molecular and cellular immunology and the biology of aging. Each proposed project represents collaborative efforts between independent investigators that will extend their individual expertise into areas that could not otherwise be effectively investigated. The four groups have been working together and will interact synergistically. Significance: These studies may ultimately lead to fundamental insights for understanding, treating or preventing the metabolic alterations and declined cognitive and immune function characteristic of elders.
Funding Period: 2009-02-15 - 2015-01-31
more information: NIH RePORT

Top Publications

  1. pmc Chaperones in autophagy
    Susmita Kaushik
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
    Pharmacol Res 66:484-93. 2012
  2. pmc Age-related oxidative stress compromises endosomal proteostasis
    Elvira S Cannizzo
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Rep 2:136-49. 2012
  3. pmc Chaperone-mediated autophagy: a unique way to enter the lysosome world
    Susmita Kaushik
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Building 504, Bronx, NY 10461, USA
    Trends Cell Biol 22:407-17. 2012
  4. pmc Regulation of lipid stores and metabolism by lipophagy
    K Liu
    Department of Medicine, Marion Bessin Liver Research Center and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Death Differ 20:3-11. 2013
  5. pmc Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy
    René L Vidal
    Faculty of Medicine, Neuroscience Biomedical Institute, University of Chile, Santiago, Chile
    Hum Mol Genet 21:2245-62. 2012
  6. pmc Inhibitory effect of dietary lipids on chaperone-mediated autophagy
    Jose Antonio Rodriguez-Navarro
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 109:E705-14. 2012
  7. pmc Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease
    Hiroshi Koga
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurosci 31:18492-505. 2011
  8. pmc Chaperone-mediated autophagy is required for tumor growth
    Maria Kon
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Sci Transl Med 3:109ra117. 2011
  9. pmc Autophagy and disease: always two sides to a problem
    Sunandini Sridhar
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Pathol 226:255-73. 2012
  10. pmc Autophagy, nutrition and immunology
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Aspects Med 33:2-13. 2012

Research Grants

  1. The Center for Native and Pacific Health Disparities Research
    MARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013

Detail Information

Publications65

  1. pmc Chaperones in autophagy
    Susmita Kaushik
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
    Pharmacol Res 66:484-93. 2012
    ..Here, we review this relatively new role of chaperones in mediating selective autophagy and comment on how alterations of this function can lead to human pathologies associated to proteotoxicity...
  2. pmc Age-related oxidative stress compromises endosomal proteostasis
    Elvira S Cannizzo
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Rep 2:136-49. 2012
    ..These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response...
  3. pmc Chaperone-mediated autophagy: a unique way to enter the lysosome world
    Susmita Kaushik
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Building 504, Bronx, NY 10461, USA
    Trends Cell Biol 22:407-17. 2012
    ....
  4. pmc Regulation of lipid stores and metabolism by lipophagy
    K Liu
    Department of Medicine, Marion Bessin Liver Research Center and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Death Differ 20:3-11. 2013
    ..Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases...
  5. pmc Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy
    René L Vidal
    Faculty of Medicine, Neuroscience Biomedical Institute, University of Chile, Santiago, Chile
    Hum Mol Genet 21:2245-62. 2012
    ..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...
  6. pmc Inhibitory effect of dietary lipids on chaperone-mediated autophagy
    Jose Antonio Rodriguez-Navarro
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 109:E705-14. 2012
    ..Our findings identify a previously unknown negative impact of high dietary lipid intake on CMA and underscore the importance of diet composition on CMA malfunction in aging...
  7. pmc Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease
    Hiroshi Koga
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurosci 31:18492-505. 2011
    ....
  8. pmc Chaperone-mediated autophagy is required for tumor growth
    Maria Kon
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Sci Transl Med 3:109ra117. 2011
    ..The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential...
  9. pmc Autophagy and disease: always two sides to a problem
    Sunandini Sridhar
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Pathol 226:255-73. 2012
    ....
  10. pmc Autophagy, nutrition and immunology
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Aspects Med 33:2-13. 2012
    ..We describe their direct effect on autophagy and discuss how the autophagic reaction to these stimuli allows cells to accommodate the requirements of the cellular response to stress, including those specific to the immune responses...
  11. pmc Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance
    Susmita Kaushik
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Metab 14:173-83. 2011
    ..Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome...
  12. pmc A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
    Hiroshi Koga
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Nat Commun 2:386. 2011
    ..Using this reporter, we find that levels of basal and inducible CMA activity are cell-type dependent, and we have identified an upregulation of this pathway in response to the catalytic inhibition of the proteasome...
  13. pmc Autophagy in the cellular energetic balance
    Rajat Singh
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Cell Metab 13:495-504. 2011
    ..This recently discovered interplay between autophagy and lipid and carbohydrate metabolism reveals the existence of a dynamic feedback between autophagy and cellular energy balance...
  14. pmc Functions of autophagy in hepatic and pancreatic physiology and disease
    Mark J Czaja
    Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Gastroenterology 140:1895-908. 2011
    ..The discovery of novel functions for this lysosomal pathway has increased our understanding of the pathophysiology of diseases in the liver and pancreas and suggested new possibilities for their treatment...
  15. pmc Autophagy and the regulation of the immune response
    Rut Valdor
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
    Pharmacol Res 66:475-83. 2012
    ..Here, we review the recent advances that have allowed us to better understand why autophagy is a crucial process in the regulation of the innate and adaptive immune responses...
  16. pmc Aging promotes the development of diet-induced murine steatohepatitis but not steatosis
    Luis Fontana
    Department of Medicine, Marion Bessin Liver Research Center, Diabetes Research Center and Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Hepatology 57:995-1004. 2013
    ..Studies of cultured hepatocytes from young and old mice revealed that aged cells were selectively sensitized to the Fas death pathway...
  17. pmc Proteostasis and the aging proteome in health and disease
    Richard I Morimoto
    Department of Molecular Biosciences, Northwestern University, Evanston, Illinois
    J Gerontol A Biol Sci Med Sci 69:S33-8. 2014
    ..Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage. ..
  18. pmc Connexins modulate autophagosome biogenesis
    Eloy Bejarano
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nat Cell Biol 16:401-14. 2014
    ..Maturation of the Cx-containing pre-autophagosomes into autophagosomes leads to degradation of these endogenous inhibitors, allowing for sustained activation of autophagy. ..
  19. pmc Chaperone-mediated autophagy: roles in disease and aging
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Building 504, Bronx, NY 10461, USA
    Cell Res 24:92-104. 2014
    ....
  20. pmc Chaperone-mediated autophagy: dedicated saviour and unfortunate victim in the neurodegeneration arena
    Jaime L Schneider
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, U S A
    Biochem Soc Trans 41:1483-8. 2013
    ....
  21. pmc Liver autophagy: much more than just taking out the trash
    Jaime L Schneider
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA
    Nat Rev Gastroenterol Hepatol 11:187-200. 2014
    ....
  22. pmc Functional interaction between autophagy and ciliogenesis
    Olatz Pampliega
    Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nature 502:194-200. 2013
    ..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. ..
  23. pmc Malfolded protein structure and proteostasis in lung diseases
    William E Balch
    1 Department of Cell Biology and Chemical Physiology, The Scripps Research Institute, La Jolla, California
    Am J Respir Crit Care Med 189:96-103. 2014
    ....
  24. doi Preventing lysosomal fat indigestion
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nat Cell Biol 15:565-7. 2013
    ..The regulators represent attractive therapeutic targets to help fight lipid-excess-associated diseases...
  25. pmc Selective autophagy: talking with the UPS
    Caroline Park
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, USA
    Cell Biochem Biophys 67:3-13. 2013
    ....
  26. pmc Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives
    Jaime Anguiano
    Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Chem Biol 9:374-82. 2013
    ..We demonstrate that chemical enhancement of CMA protects cells from oxidative stress and from proteotoxicity, supporting a potential therapeutic opportunity when reduced CMA contributes to cellular dysfunction and disease...
  27. pmc Balance between autophagic pathways preserves retinal homeostasis
    Natalia Rodríguez-Muela
    Department of Cellular and Molecular Biology, CIB, CSIC, Ramiro de Maeztu 9, E 28040, Madrid, Spain
    Aging Cell 12:478-88. 2013
    ..Our results show for the first time a cross talk of different lysosomal proteolytic systems in the retina during normal aging and may help the development of new therapeutic intervention for age-dependent retinal diseases...
  28. pmc Interplay of LRRK2 with chaperone-mediated autophagy
    Samantha J Orenstein
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Neurosci 16:394-406. 2013
    ..This newly described LRRK2 self-perpetuating inhibitory effect on CMA could underlie toxicity in Parkinson's disease by compromising the degradation of α-synuclein, another Parkinson's disease-related protein degraded by this pathway...
  29. pmc The lipid kinase PI4KIIIβ preserves lysosomal identity
    Sunandini Sridhar
    Department of Development and Molecular Biology, Bronx, NY 10461, USA
    EMBO J 32:324-39. 2013
    ....
  30. pmc Molecular determinants of selective clearance of protein inclusions by autophagy
    Esther Wong
    School of Biological Sciences, Nanyang Technological University, SBS 03n 05, 60 Nanyang Drive, Singapore 637551, Singapore
    Nat Commun 3:1240. 2012
    ....
  31. pmc Autophagy in nonalcoholic steatohepatitis
    Muhammad Amir
    Department of Medicine, Marion Bessin Liver Research Center and Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Expert Rev Gastroenterol Hepatol 5:159-66. 2011
    ..The impairment in autophagy that occurs with cellular lipid accumulation, obesity and aging may therefore have an important impact on this disease, and agents to augment hepatic autophagy have therapeutic potential in NASH...
  32. pmc Regulation of lipid droplets by autophagy
    Hanqing Dong
    Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Trends Endocrinol Metab 22:234-40. 2011
    ..Pathophysiological changes in autophagic function can alter cellular lipid metabolism and promote disease states. Autophagy therefore represents a new cellular target for abnormalities in lipid metabolism and accumulation...
  33. pmc Protein homeostasis and aging: The importance of exquisite quality control
    Hiroshi Koga
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Ageing Res Rev 10:205-15. 2011
    ..In this work, we review recent advances on our understanding of the contribution of chaperones and proteolytic systems to the maintenance of cellular homeostasis, the cellular response to stress and ultimately to longevity...
  34. pmc Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications
    Mark J Czaja
    Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Am J Physiol Cell Physiol 298:C973-8. 2010
    ..The findings also suggest possible new therapeutic approaches to the problems of lipid overaccumulation and impaired autophagy that occur with aging and the metabolic syndrome...
  35. pmc HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy
    Joo Yong Lee
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    EMBO J 29:969-80. 2010
    ..Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome-lysosome fusion...
  36. pmc IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome
    Leslie Michels Thompson
    Department of Psychiatry and Human Behavior, University of California, Irvine, 92697, USA
    J Cell Biol 187:1083-99. 2009
    ..Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species...
  37. pmc Chaperone-mediated autophagy in health and disease
    Maria Kon
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    FEBS Lett 584:1399-404. 2010
    ..Here we review the unique properties of CMA compared to other autophagic pathways and its relevance in health and disease...
  38. ncbi Synergy and antagonism of macroautophagy and chaperone-mediated autophagy in a cell model of pathological tau aggregation
    Yipeng Wang
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    Autophagy 6:182-3. 2010
    ..The Tau aggregates are removed from cells by macroautophagy. Thus the two autophagic pathways could become possible therapeutic targets...
  39. pmc Chaperone-mediated autophagy: selectivity pays off
    Ana Maria Cuervo
    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
    Trends Endocrinol Metab 21:142-50. 2010
    ..Prevention of the age-dependent decline in CMA has major beneficial effects on cellular and organ homeostasis and function, revealing that CMA is an essential component of the anti-aging fight...
  40. pmc Autophagy regulates adipose mass and differentiation in mice
    Rajat Singh
    Department of Medicine, Albert Einstein College of Medicine, New York, New York10461, USA
    J Clin Invest 119:3329-39. 2009
    ..Autophagy therefore functions to regulate body lipid accumulation by controlling adipocyte differentiation and determining the balance between white and brown fat...
  41. pmc XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy
    Claudio Hetz
    Institute of Biomedical Sciences, The FONDAP Center for Molecular Studies of the Cell CEMC and the Millennium Nucleus for Neural Morphogenesis NEMO, University of Chile, Santiago, Chile
    Genes Dev 23:2294-306. 2009
    ..Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration...
  42. pmc Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
    Yipeng Wang
    Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany
    Hum Mol Genet 18:4153-70. 2009
    ....
  43. pmc Autophagy regulates lipid metabolism
    Rajat Singh
    Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Nature 458:1131-5. 2009
    ..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...
  44. ncbi Methods to monitor chaperone-mediated autophagy
    Susmita Kaushik
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, USA
    Methods Enzymol 452:297-324. 2009
    ..In this chapter we review the different experimental approaches used to assess CMA activity both in cells in culture and in different organs from animals...
  45. pmc Autophagy and aging: keeping that old broom working
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann B 611, Bronx, NY 10461, USA
    Trends Genet 24:604-12. 2008
    ..Here, I review the recent genetic evidence in support of tight connections between autophagy, health span and aging...
  46. pmc Chaperone-mediated autophagy
    Eloy Bejarano
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Am Thorac Soc 7:29-39. 2010
    ....
  47. pmc Chaperone-mediated autophagy: molecular mechanisms and physiological relevance
    Samantha J Orenstein
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Semin Cell Dev Biol 21:719-26. 2010
    ..Changes with age in CMA activity and the contribution of failure of CMA to the phenotype of aging and to the pathogenesis of several age-related pathologies are also described...
  48. pmc Microautophagy of cytosolic proteins by late endosomes
    Ranjit Sahu
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Dev Cell 20:131-9. 2011
    ..Therefore, we propose that endosomal microautophagy shares molecular components with both the endocytic and autophagic pathways...
  49. pmc Chaperone-mediated autophagy in protein quality control
    Esperanza Arias
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Curr Opin Cell Biol 23:184-9. 2011
    ..In fact, CMA activation seems to be a common mechanism of cellular defense against proteotoxicity...
  50. pmc Integration of clearance mechanisms: the proteasome and autophagy
    Esther Wong
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Cold Spring Harb Perspect Biol 2:a006734. 2010
    ....
  51. pmc Macroautophagy regulates energy metabolism during effector T cell activation
    Vanessa M Hubbard
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Immunol 185:7349-57. 2010
    ..These results suggest that macroautophagy is an actively regulated process in T cells that can be induced in response to TCR engagement to accommodate the bioenergetic requirements of activated T cells...
  52. pmc Autophagic pathways and metabolic stress
    S Kaushik
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Diabetes Obes Metab 12:4-14. 2010
    ..We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders...
  53. pmc Identification of regulators of chaperone-mediated autophagy
    Urmi Bandyopadhyay
    Department of Development and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Cell 39:535-47. 2010
    ..The dynamic interactions of these two proteins at the lysosomal membrane unveil now a role for GTP as a negative regulator of CMA...
  54. ncbi Autophagy and lipids: tightening the knot
    Jose Antonio Rodriguez-Navarro
    Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA
    Semin Immunopathol 32:343-53. 2010
    ..In addition, we comment on the regulatory role that lipid molecules and their modifying enzymes play on different steps of the autophagic process...
  55. pmc Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration
    Hiroshi Koga
    Department of Developmental and Molecular Biology, Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA
    Neurobiol Dis 43:29-37. 2011
    ..This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."..
  56. pmc Autophagy gone awry in neurodegenerative diseases
    Esther Wong
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Neurosci 13:805-11. 2010
    ....
  57. pmc Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress
    Yongjun Wang
    Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Hepatology 52:266-77. 2010
    ..CMA inhibition sensitized cells to death from menadione through a mechanism different from that of a loss of macroautophagy, because death occurred in the absence of JNK/c-Jun overactivation or ATP depletion...
  58. pmc Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease
    Marta Martinez-Vicente
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Neurosci 13:567-76. 2010
    ..We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells...
  59. pmc Altered lipid content inhibits autophagic vesicular fusion
    Hiroshi Koga
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
    FASEB J 24:3052-65. 2010
    ..Changes in the intracellular lipid content (i.e., metabolic disorders) may thus have pronounced effects on the fusion step of macroautophagy and affect the overall activity of this intracellular proteolytic pathway...
  60. ncbi Protein degradation, aggregation, and misfolding
    Ana Maria Cuervo
    Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Mov Disord 25:S49-54. 2010
    ....
  61. pmc Chaperone-mediated autophagy
    S Kaushik
    Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USA
    Methods Mol Biol 445:227-44. 2008
    ..However, the most unequivocal method to measure CMA is by directly tracking the translocation of substrate proteins into isolated lysosomes...

Research Grants30

  1. The Center for Native and Pacific Health Disparities Research
    MARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013
    ..5) To prepare and empower our diverse Native and Pacific People communities to take ownership of their own health and wellness. ..