Autophagy and Aging

  • Nuria Martinez-Lopez
  • Diana Athonvarangkul
  • Rajat SinghEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 847)


Autophagy is a critical quality control pathway that is conserved across diverse systems ranging from simple unicellular organisms like yeast to more complex systems, for instance mammals. Although, the fundamental role of autophagy is to maintain cellular quality control through lysosomal degradation of unwanted proteins and organelles, recent studies have mapped several new functions of this pathway that range from fuel utilization, cellular differentiation to protection against cell death. Given the importance of this pathway in maintaining cellular homeostasis, it has been considered that compromised autophagy could contribute to several of the commonly observed age-associated pathologies including neurodegeneration, reduction of muscle mass, cardiac malfunction, excessive lipid accumulation in tissues and glucose intolerance. The present chapter describes the two best-characterized autophagy pathways—macroautophagy and chaperone-mediated autophagy, and discusses how changes in these pathways associate with age-associated disorders. Understanding how to maintain “clean cells” by activation of autophagy could be an attractive strategy to maintain healthspan in aged individuals.


Autophagy Aging Macroautophagy apparatus Signaling pathways Macroautophagy Chaperone-mediated autophagy 



We thankfully acknowledge NIH grants, DK087776 and AG043517, and an Ellison Medical Foundation award to RS. DA is supported by training grants 5T32GM728837 and T32GM007288. We thank Dr. Susmita Kaushik for assisting with designs of the models in Figs. 3.1 and 3.2.


  1. 1.
    Arias E, Cuervo AM (2011) Chaperone-mediated autophagy in protein quality control. Curr Opin Cell Biol 23(2):184–189CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM (2008) The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol Cell Biol 28(18):5747–5763CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM (2010) Identification of regulators of chaperone-mediated autophagy. Mol Cell 39(4):535–547CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Bergamini E, Del Roso A, Fierabracci V, Gori Z, Masiello P, Masini M, Pollera M (1993) A new method for the investigation of endocrine-regulated autophagy and protein degradation in rat liver. Exp Mol Pathol 59(1):13–26CrossRefPubMedGoogle Scholar
  5. 5.
    Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW 4th (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456(7219):259–263CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Chauhan S, Goodwin JG, Chauhan S, Manyam G, Wang J, Kamat AM, Boyd DD (2013) ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell 50(1):16–28CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Cornu M, Albert V, Hall MN (2013) mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev 23(1):53–62CrossRefPubMedGoogle Scholar
  9. 9.
    Cuervo AM (2008) Autophagy and aging: keeping that old broom working. Trends Genet 24(12):604–612CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Cuervo AM (2010) Chaperone-mediated autophagy: selectivity pays off. Trends Endocrinol Metab 21(3):142–150CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Cuervo AM, Dice JF (2000) Age-related decline in chaperone-mediated autophagy. J Biol Chem 275(40):31505–31513CrossRefPubMedGoogle Scholar
  12. 12.
    Cuervo AM, Wong E (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24(1):92–104CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Cuervo AM, Knecht E, Terlecky SR, Dice JF (1995) Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am J Physiol 269(5 Pt 1):C1200–1208PubMedGoogle Scholar
  14. 14.
    Cuervo AM, Dice JF, Knecht E (1997) A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272(9):5606–5615CrossRefPubMedGoogle Scholar
  15. 15.
    Cuervo AM, Mann L, Bonten EJ, d’Azzo A, Dice JF (2003) Cathepsin A regulates chaperone-mediated autophagy through cleavage of the lysosomal receptor. EMBO J 22(1):47–59CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Decressac M, Mattsson B, Weikop P, Lundblad M, Jakobsson J, Bjorklund A (2013) TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci U S A 110(19):E1817–1826CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Del Roso A, Bombara M, Fierabracci V, Masini M, Masiello P, Pollera M, Bergamini E (1991) Effect of dietary restriction on the age-related changes in hormone-regulated protein breakdown. Aging (Milano) 3(4):407–408Google Scholar
  18. 18.
    Del Roso A, Vittorini S, Cavallini G, Donati A, Gori Z, Masini M, Pollera M, Bergamini E (2003) Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis. Exp Gerontol 38(5):519–527CrossRefPubMedGoogle Scholar
  19. 19.
    Donati A, Cavallini G, Paradiso C, Vittorini S, Pollera M, Gori Z, Bergamini E (2001) Age-related changes in the autophagic proteolysis of rat isolated liver cells: effects of antiaging dietary restrictions. J Gerontol A Biol Sci Med Sci 56(9):B375–383CrossRefPubMedGoogle Scholar
  20. 20.
    Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) “PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12(2):119–131CrossRefPubMedGoogle Scholar
  22. 22.
    Geng J, Klionsky DJ (2008) The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep 9(9):859–864CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F, Ohsumi Y (2007) The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282(52):37298–37302CrossRefPubMedGoogle Scholar
  24. 24.
    Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889CrossRefPubMedGoogle Scholar
  25. 25.
    Hardie DG, Carling D, Halford N (1994) Roles of the Snf1/Rkin1/AMP-activated protein kinase family in the response to environmental and nutritional stress. Semin Cell Biol 5(6):409–416CrossRefPubMedGoogle Scholar
  26. 26.
    Harding TM, Hefner-Gravink A, Thumm M, Klionsky DJ (1996) Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway. J Biol Chem 271(30):17621–17624CrossRefPubMedGoogle Scholar
  27. 27.
    Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395PubMedCentralPubMedGoogle Scholar
  28. 28.
    He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Ichimura Y, Waguri S, Sou YS, Kageyama S, Hasegawa J, Ishimura R, Saito T, Yang Y, Kouno T, Fukutomi T, Hoshii T, Hirao A, Takagi K, Mizushima T, Motohashi H, Lee MS, Yoshimori T, Tanaka K, Yamamoto M, Komatsu M (2013) Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell 51(5):618–631CrossRefPubMedGoogle Scholar
  30. 30.
    Itakura E, Kishi-Itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151(6):1256–1269CrossRefPubMedGoogle Scholar
  31. 31.
    Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493(7432):338–345CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Kaushik S, Massey AC, Cuervo AM (2006) Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated autophagy. EMBO J 25(17):3921–3933CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Kaushik S, Arias E, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, Schwartz GJ, Pessin JE, Singh R (2012) Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Rep 13(3):258–265CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Kiffin R, Kaushik S, Zeng M, Bandyopadhyay U, Zhang C, Massey AC, Martinez-Vicente M, Cuervo AM (2007) Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J Cell Sci 120(Pt 5):782–791CrossRefPubMedGoogle Scholar
  35. 35.
    Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462(2):245–253CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13(2):132–141CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Koga H, Kaushik S, Cuervo AM (2010) Altered lipid content inhibits autophagic vesicular fusion. FASEB J 24(8):3052–3065CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, Chiba T (2005) Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 169(3):425–434CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884CrossRefPubMedGoogle Scholar
  40. 40.
    Kroemer G, Levine B (2008) Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 9(12):1004–1010CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Lapierre LR, De Magalhaes Filho CD, McQuary PR, Chu CC, Visvikis O, Chang JT, Gelino S, Ong B, Davis AE, Irazoqui JE, Dillin A, Hansen M (2013) The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun 4:2267PubMedGoogle Scholar
  42. 42.
    Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A 105(9):3374–3379CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132(1):27–42CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402(6762):672–676CrossRefPubMedGoogle Scholar
  45. 45.
    Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan J (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A 107(32):14164–14169CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Martinez-Lopez N, Athonvarangkul D, Sahu S, Coletto L, Zong H, Bastie CC, Pessin JE, Schwartz GJ, Singh R (2013) Autophagy in Myf5 + progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development. EMBO Rep 14(9):795–803CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, Kaushik S, de Vries R, Arias E, Harris S, Sulzer D, Cuervo AM (2010) Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease. Nat Neurosci 13(5):567–576CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M (2009) Autophagy is required to maintain muscle mass. Cell Metab 10(6):507–515CrossRefPubMedGoogle Scholar
  49. 49.
    Matecic M, Smith DL, Pan X, Maqani N, Bekiranov S, Boeke JD, Smith JS (2010) A microarray-based genetic screen for yeast chronological aging factors. PLoS Genet 6(4):e1000921CrossRefPubMedCentralPubMedGoogle Scholar
  50. 50.
    Matsui A, Kamada Y, Matsuura A (2013) The role of autophagy in genome stability through suppression of abnormal mitosis under starvation. PLoS Genet 9(1):e1003245CrossRefPubMedCentralPubMedGoogle Scholar
  51. 51.
    Nezis IP, Stenmark H (2012) p62 at the interface of autophagy, oxidative stress signaling, and cancer. Antioxid Redox Signal 17(5):786–793CrossRefPubMedGoogle Scholar
  52. 52.
    Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282(33):24131–24145CrossRefPubMedGoogle Scholar
  53. 53.
    Papinski D, Kraft C (2014) Atg1 kinase organizes autophagosome formation by phosphorylating Atg9. Autophagy 10(7):1338–1340CrossRefPubMedGoogle Scholar
  54. 54.
    Phillips AR, Suttangkakul A, Vierstra RD (2008) The ATG12-conjugating enzyme ATG10 Is essential for autophagic vesicle formation in Arabidopsis thaliana. Genetics 178(3):1339–1353CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300CrossRefPubMedCentralPubMedGoogle Scholar
  56. 56.
    Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O’Kane CJ, Rubinsztein DC (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36(6):585–595CrossRefPubMedGoogle Scholar
  57. 57.
    Rea SL, Majcher V, Searle MS, Layfield R (2014) SQSTM1 mutations-bridging Paget disease of bone and ALS/FTLD. Exp Cell Res 325(1):27–37CrossRefPubMedGoogle Scholar
  58. 58.
    Rodriguez-Navarro JA, Kaushik S, Koga H, Dall’Armi C, Shui G, Wenk MR, Di Paolo G, Cuervo AM (2012) Inhibitory effect of dietary lipids on chaperone-mediated autophagy. Proc Natl Acad Sci U S A 109(12):E705–714CrossRefPubMedCentralPubMedGoogle Scholar
  59. 59.
    Romanov J, Walczak M, Ibiricu I, Schuchner S, Ogris E, Kraft C, Martens S (2012) Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation. EMBO J 31(22):4304–4317CrossRefPubMedCentralPubMedGoogle Scholar
  60. 60.
    Rubinsztein DC, Marino G, Kroemer G (2011) Autophagy and aging. Cell 146(5):682–695CrossRefPubMedGoogle Scholar
  61. 61.
    Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L (2011) Microautophagy of cytosolic proteins by late endosomes. Dev Cell 20(1):131–139CrossRefPubMedCentralPubMedGoogle Scholar
  62. 62.
    Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M (1997) AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae. J Bacteriol 179(4):1068–1076PubMedCentralPubMedGoogle Scholar
  63. 63.
    Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A (2011) TFEB links autophagy to lysosomal biogenesis. Science 332(6036):1429–1433CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Erdin S, Huynh T, Ferron M, Karsenty G, Vellard MC, Facchinetti V, Sabatini DM, Ballabio A (2012) A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J 31(5):1095–1108CrossRefPubMedCentralPubMedGoogle Scholar
  65. 65.
    Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4(2):176–184CrossRefPubMedGoogle Scholar
  66. 66.
    Singh R, Cuervo AM (2011) Autophagy in the cellular energetic balance. Cell Metab 13(5):495–504CrossRefPubMedCentralPubMedGoogle Scholar
  67. 67.
    Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ (2009) Autophagy regulates lipid metabolism. Nature 458(7242):1131–1135CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Spampanato C, Feeney E, Li L, Cardone M, Lim JA, Annunziata F, Zare H, Polishchuk R, Puertollano R, Parenti G, Ballabio A, Raben N (2013) Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol Med 5(5):691–706CrossRefPubMedCentralPubMedGoogle Scholar
  69. 69.
    Stroikin Y, Dalen H, Loof S, Terman A (2004) Inhibition of autophagy with 3-methyladenine results in impaired turnover of lysosomes and accumulation of lipofuscin-like material. Eur J Cell Biol 83(10):583–590CrossRefPubMedGoogle Scholar
  70. 70.
    Tanida I, Tanida-Miyake E, Ueno T, Kominami E (2001) The human homolog of Saccharomyces cerevisiae Apg7p is a protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J Biol Chem 276(3):1701–1706CrossRefPubMedGoogle Scholar
  71. 71.
    Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36(12):2503–2518CrossRefPubMedGoogle Scholar
  72. 72.
    Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4(3):330–338CrossRefPubMedGoogle Scholar
  73. 73.
    Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333(1–2):169–174CrossRefPubMedGoogle Scholar
  74. 74.
    Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30(6):678–688CrossRefPubMedCentralPubMedGoogle Scholar
  75. 75.
    Yang Z, Ming XF (2012) mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases. Obes Rev 13(Suppl 2):58–68CrossRefPubMedGoogle Scholar
  76. 76.
    Yang L, Li P, Fu S, Calay ES, Hotamisligil GS (2010) Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 11(6):467–478CrossRefPubMedCentralPubMedGoogle Scholar
  77. 77.
    Yang SB, Tien AC, Boddupalli G, Xu AW, Jan YN, Jan LY (2012) Rapamycin ameliorates age-dependent obesity associated with increased mTOR signaling in hypothalamic POMC neurons. Neuron 75(3):425–436CrossRefPubMedCentralPubMedGoogle Scholar
  78. 78.
    Young AR, Chan EY, Hu XW, Kochl R, Crawshaw SG, High S, Hailey DW, Lippincott-Schwartz J, Tooze SA (2006) Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 119(Pt 18):3888–3900CrossRefPubMedGoogle Scholar
  79. 79.
    Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14(9):959–965CrossRefPubMedCentralPubMedGoogle Scholar
  80. 80.
    Zhao Z, Oh S, Li D, Ni D, Pirooz SD, Lee JH, Yang S, Lee JY, Ghozalli I, Costanzo V, Stark JM, Liang C (2012) A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Dev Cell 22(5):1001–1016CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Nuria Martinez-Lopez
    • 1
  • Diana Athonvarangkul
    • 1
  • Rajat Singh
    • 2
    Email author
  1. 1.Department of Medicine and Department of Molecular PharmacologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of Medicine (Endocrinology), and Molecular PharmacologyDiabetes Research Center, Albert Einstein College of MedicineBronxUSA

Personalised recommendations