Skip to main content
SpringerLink
Log in

Emerging roles of autophagy in metabolism and metabolic disorders

  • Review
  • Published:
Frontiers in Biology

Abstract

The global prevalence of metabolic disorders is an immediate threat to human health. Genetic features, environmental aspects and lifestyle changes are the major risk factors determining metabolic dysfunction in the body. Autophagy is a housekeeping stress-induced lysosomal degradation pathway, which recycles macromolecules and metabolites for new protein synthesis and energy production and regulates cellular homeostasis by clearance of damaged protein or organelles. Recently, a dramatically increasing number of literatures has shown that defects of the autophagic machinery is associated with dysfunction of multiple metabolic tissues including pancreatic β cells, liver, adipose tissue and muscle, and is implicated in metabolic disorders such as obesity and insulin resistance. Here in this review, we summarize the representative works on these topics and discuss the versatile roles of autophagy in the regulation of cellular metabolism and its possible implication in metabolic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Axe E L, Walker S A, Manifava M, Chandra P, Roderick H L, Habermann A, Griffiths G, Ktistakis N T (2008). Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol, 182(4): 685–701

    PubMed Central  CAS  PubMed  Google Scholar 

  • Baerga R, Zhang Y, Chen P H, Goldman S, Jin S (2009). Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy, 5(8): 1118–1130

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Øvervatn A, Stenmark H, Johansen T (2005). p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol, 171(4): 603–614

    PubMed Central  PubMed  Google Scholar 

  • Boyle K B, Randow F (2013). The role of ‘eat-me’ signals and autophagy cargo receptors in innate immunity. Curr Opin Microbiol, 16(3): 339–348

    CAS  PubMed  Google Scholar 

  • Burman C, Ktistakis N T (2010). Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett, 584(7): 1302–1312

    CAS  PubMed  Google Scholar 

  • Campello S, Strappazzon F, Cecconi F (2014). Mitochondrial dismissal in mammals, from protein degradation to mitophagy. Biochim Biophys Acta, 1837(4): 451–460

    CAS  PubMed  Google Scholar 

  • Cebollero E, Reggiori F, Kraft C (2012). Reticulophagy and ribophagy: regulated degradation of protein production factories. Int J Cell Biol, 2012: 182834

    PubMed Central  PubMed  Google Scholar 

  • Cecconi F, Levine B (2008). The role of autophagy in mammalian development: cell makeover rather than cell death. Dev Cell, 15(3): 344–357

    PubMed Central  CAS  PubMed  Google Scholar 

  • Coupé B, Ishii Y, Dietrich M O, Komatsu M, Horvath T L, Bouret S G (2012). Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metab, 15(2): 247–255

    PubMed Central  PubMed  Google Scholar 

  • De Duve C, Wattiaux R (1966). Functions of lysosomes. Annu Rev Physiol, 28(1): 435–492

    PubMed  Google Scholar 

  • Ebato C, Uchida T, Arakawa M, Komatsu M, Ueno T, Komiya K, Azuma K, Hirose T, Tanaka K, Kominami E, Kawamori R, Fujitani Y, Watada H (2008). Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab, 8(4): 325–332

    CAS  PubMed  Google Scholar 

  • Elzinga B M, Nyhan M J, Crowley L C, O’Donovan T R, Cahill M R, McKenna S L (2013). Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein. Am J Hematol, 88(6): 455–462

    CAS  PubMed  Google Scholar 

  • Geisler S, Holmström K M, Skujat D, Fiesel F C, Rothfuss O C, Kahle P J, Springer W (2010). PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol, 12(2): 119–131

    CAS  PubMed  Google Scholar 

  • Geng J, Klionsky D J (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep, 9(9): 859–864

    PubMed Central  CAS  PubMed  Google Scholar 

  • Goldman S, Zhang Y, Jin S (2010). Autophagy and adipogenesis: implications in obesity and type II diabetes. Autophagy, 6(1): 179–181

    PubMed Central  PubMed  Google Scholar 

  • Gonzalez C D, Lee M S, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, Watada H, Wiley JW (2011). The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy, 7(1): 2–11

    PubMed Central  CAS  PubMed  Google Scholar 

  • Grumati P, Coletto L, Schiavinato A, Castagnaro S, Bertaggia E, Sandri M, Bonaldo P (2011). Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy, 7(12): 1415–1423

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guariguata L, Whiting D R, Hambleton I, Beagley J, Linnenkamp U, Shaw J E (2014). Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract, 103(2): 137–149

    CAS  PubMed  Google Scholar 

  • Hanada T, Noda N N, 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): 37298–37302

    CAS  PubMed  Google Scholar 

  • Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan J L, Mizushima N (2008). FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol, 181(3): 497–510

    PubMed Central  CAS  PubMed  Google Scholar 

  • He C, Bassik M C, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May H I, Hill J A, Virgin H W, Gilpin C, Xiao G, Bassel-Duby R, Scherer P E, Levine B (2012). Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature, 481(7382): 511–515

    PubMed Central  CAS  PubMed  Google Scholar 

  • He C, Wei Y, Sun K, Li B, Dong X, Zou Z, Liu Y, Kinch L N, Khan S, Sinha S, Xavier R J, Grishin N V, Xiao G, Eskelinen E L, Scherer P E, Whistler J L, Levine B (2013). Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell, 154(5): 1085–1099

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ichimura Y, Waguri S, Sou Y S, 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 M S, Yoshimori T, Tanaka K, Yamamoto M, Komatsu M (2013). Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell, 51(5): 618–631

    CAS  PubMed  Google Scholar 

  • Jaber N, Dou Z, Chen J S, Catanzaro J, Jiang Y P, Ballou L M, Selinger E, Ouyang X, Lin R Z, Zhang J, Zong W X (2012). Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci USA, 109(6): 2003–2008

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jeong H, Then F, Melia T J Jr, Mazzulli J R, Cui L, Savas J N, Voisine C, Paganetti P, Tanese N, Hart A C, Yamamoto A, Krainc D (2009). Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 137(1): 60–72

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang S, Heller B, Tagliabracci V S, Zhai L, Irimia JM, DePaoli-Roach A A, Wells C D, Skurat A V, Roach P J (2010). Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J Biol Chem, 285(45): 34960–34971

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang S, Wells C D, Roach P J (2011). Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochem Biophys Res Commun, 413(3): 420–425

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang Y, Huang W, Wang J, Xu Z, He J, Lin X, Zhou Z, Zhang J (2014). Metformin plays a dual role in MIN6 pancreatic β cell function through AMPK-dependent autophagy. Int J Biol Sci, 10(3): 268–277

    PubMed Central  PubMed  Google Scholar 

  • Johansen T, Lamark T (2011). Selective autophagy mediated by autophagic adapter proteins. Autophagy, 7(3): 279–296

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jung C H, Jun C B, Ro S H, Kim Y M, Otto N M, Cao J, Kundu M, Kim D H (2009). ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell, 20(7): 1992–2003

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jung C H, Ro S H, Cao J, Otto N M, Kim D H (2010). mTOR regulation of autophagy. FEBS Lett, 584(7): 1287–1295

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jung H S, Chung K W, Won Kim J, Kim J, Komatsu M, Tanaka K, Nguyen Y H, Kang T M, Yoon K H, Kim J W, Jeong Y T, Han M S, Lee M K, Kim K W, Shin J, Lee M S (2008). Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab, 8(4): 318–324

    CAS  PubMed  Google Scholar 

  • Jung H S, Lee M S (2010). Role of autophagy in diabetes and mitochondria. Ann N Y Acad Sci, 1201(1): 79–83

    CAS  PubMed  Google Scholar 

  • Kageyama S, Sou Y S, Uemura T, Kametaka S, Saito T, Ishimura R, Kouno T, Bedford L, Mayer R J, Lee M S, Yamamoto M, Waguri S, Tanaka K, Komatsu M (2014). Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway. J Biol Chem, 289(36): 24944–24955

    CAS  PubMed  Google Scholar 

  • Kahn S E, Hull R L, Utzschneider K M (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 444(7121): 840–846

    CAS  PubMed  Google Scholar 

  • Kalender A, Selvaraj A, Kim S Y, Gulati P, Brûlé S, Viollet B, Kemp B E, Bardeesy N, Dennis P, Schlager J J, Marette A, Kozma S C, Thomas G (2010). Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab, 11(5): 390–401

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kane L A, Lazarou M, Fogel A I, Li Y, Yamano K, Sarraf S A, Banerjee S, Youle R J (2014). PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol, 205(2): 143–153

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kaushik S, Arias E, Kwon H, Lopez N M, Athonvarangkul D, Sahu S, Schwartz G J, Pessin J E, Singh R (2012). Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Rep, 13(3): 258–265

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kaushik S, Cuervo A M (2012). Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol, 22(8): 407–417

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kaushik S, Rodriguez-Navarro J A, Arias E, Kiffin R, Sahu S, Schwartz G J, Cuervo AM, Singh R (2011). Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab, 14(2): 173–183

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kazlauskaite A, Kondapalli C, Gourlay R, Campbell D G, Ritorto M S, Hofmann K, Alessi D R, Knebel A, Trost M, Muqit M M (2014). Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J, 460(1): 127–139

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kim K H, Jeong Y T, Oh H, Kim S H, Cho JM, Kim Y N, Kim S S, Kim H, Hur K Y, Kim H K, Ko T, Han J, Kim H L, Kim J, Back S H, Komatsu M, Chen H, Chan D C, Konishi M, Itoh N, Choi C S, Lee M S (2013). Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine. Nat Med, 19(1): 83–92

    CAS  PubMed  Google Scholar 

  • Kim K H, Lee M S (2014). Autophagy—a key player in cellular and body metabolism. Nat Rev Endocrinol, 10(6): 322–337

    CAS  PubMed  Google Scholar 

  • Kirkin V, Lamark T, Sou Y S, Bjørkøy G, Nunn J L, Bruun J A, Shvets E, McEwan D G, Clausen T H, Wild P, Bilusic I, Theurillat J P, Øvervatn A, Ishii T, Elazar Z, Komatsu M, Dikic I, Johansen T (2009). A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell, 33(4): 505–516

    CAS  PubMed  Google Scholar 

  • Knaevelsrud H, Simonsen A (2010). Fighting disease by selective autophagy of aggregate-prone proteins. FEBS Lett, 584(12): 2635–2645

    CAS  PubMed  Google Scholar 

  • Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou Y S, Ueno I, Sakamoto A, Tong K I, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M (2010). The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol, 12(3): 213–223

    CAS  PubMed  Google Scholar 

  • 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): 425–434

    PubMed Central  CAS  PubMed  Google Scholar 

  • Korac J, Schaeffer V, Kovacevic I, Clement A M, Jungblut B, Behl C, Terzic J, Dikic I (2013). Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J Cell Sci, 126(Pt 2): 580–592

    PubMed Central  CAS  PubMed  Google Scholar 

  • Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon E A, Trempe J F, Saeki Y, Tanaka K, Matsuda N (2014). Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature, 510(7503): 162–166

    CAS  PubMed  Google Scholar 

  • Kraft C, Deplazes A, Sohrmann M, Peter M (2008). Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol, 10(5): 602–610

    CAS  PubMed  Google Scholar 

  • Kroemer G, Mariño G, Levine B (2010). Autophagy and the integrated stress response. Mol Cell, 40(2): 280–293

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kuma A, Mizushima N (2010). Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism. Semin Cell Dev Biol, 21(7): 683–690

    CAS  PubMed  Google Scholar 

  • Le Guezennec X, Brichkina A, Huang Y F, Kostromina E, Han W, Bulavin D V (2012). Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metab, 16(1): 68–80

    PubMed  Google Scholar 

  • Lee J M, Wagner M, Xiao R, Kim K H, Feng D, Lazar M A, Moore D D (2014). Nutrient-sensing nuclear receptors coordinate autophagy. Nature, 516(7529): 112–115

    CAS  PubMed  Google Scholar 

  • Levine B, Klionsky D J (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell, 6(4): 463–477

    CAS  PubMed  Google Scholar 

  • Levine B, Kroemer G (2008). Autophagy in the pathogenesis of disease. Cell, 132(1): 27–42

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lim Y M, Lim H, Hur K Y, Quan W, Lee H Y, Cheon H, Ryu D, Koo S H, Kim H L, Kim J, Komatsu M, Lee M S (2014). Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes. Nat Commun, 5: 4934

    CAS  PubMed  Google Scholar 

  • Lira V A, Okutsu M, Zhang M, Greene N P, Laker R C, Breen D S, Hoehn K L, Yan Z (2013). Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J, 27: 4184–4193

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu H Y, Han J, Cao S Y, Hong T, Zhuo D, Shi J, Liu Z, Cao W (2009). Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem, 284(45): 31484–31492

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden S J, Di Lisi R, Sandri C, Zhao J, Goldberg A L, Schiaffino S, Sandri M (2007). FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab, 6(6): 458–471

    CAS  PubMed  Google Scholar 

  • Marselli L, Bugliani M, Suleiman M, Olimpico F, Masini M, Petrini M, Boggi U, Filipponi F, Syed F, Marchetti P (2013). β-Cell inflammation in human type 2 diabetes and the role of autophagy. Diabetes Obes Metab, 15(Suppl 3): 130–136

    CAS  PubMed  Google Scholar 

  • 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): 507–515

    CAS  PubMed  Google Scholar 

  • Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T (2009). Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol, 11(4): 385–396

    CAS  PubMed  Google Scholar 

  • Mizushima N (2010). The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol, 22(2): 132–139

    CAS  PubMed  Google Scholar 

  • Mizushima N, Komatsu M (2011). Autophagy: renovation of cells and tissues. Cell, 147(4): 728–741

    CAS  PubMed  Google Scholar 

  • Mizushima N, Yoshimori T, Ohsumi Y (2011). The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol, 27(1): 107–132

    CAS  PubMed  Google Scholar 

  • Narendra D, Tanaka A, Suen D F, Youle R J (2008). Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol, 183(5): 795–803

    PubMed Central  CAS  PubMed  Google Scholar 

  • Newgard C B, An J, Bain J R, Muehlbauer M J, Stevens R D, Lien L F, Haqq A M, Shah S H, Arlotto M, Slentz C A, Rochon J, Gallup D, Ilkayeva O, Wenner B R, Yancy W S Jr, Eisenson H, Musante G, Surwit R S, Millington D S, Butler M D, Svetkey L P (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab, 9(4): 311–326

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ogawa M, Yoshikawa Y, Kobayashi T, Mimuro H, Fukumatsu M, Kiga K, Piao Z, Ashida H, Yoshida M, Kakuta S, Koyama T, Goto Y, Nagatake T, Nagai S, Kiyono H, Kawalec M, Reichhart J M, Sasakawa C (2011). A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe, 9(5): 376–389

    CAS  PubMed  Google Scholar 

  • Ossareh-Nazari B, Niño C A, Bengtson M H, Lee J W, Joazeiro C A, Dargemont C (2014). Ubiquitylation by the Ltn1 E3 ligase protects 60S ribosomes from starvation-induced selective autophagy. J Cell Biol, 204(6): 909–917

    PubMed Central  PubMed  Google Scholar 

  • Ouimet M, Franklin V, Mak E, Liao X, Tabas I, Marcel Y L (2011). Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab, 13(6): 655–667

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pankiv S, Clausen T H, Lamark T, Brech A, Bruun J A, Outzen H, Øvervatn A, Bjørkøy 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): 24131–24145

    CAS  PubMed  Google Scholar 

  • Pattingre S, Tassa A, Qu X, Garuti R, Liang X H, Mizushima N, Packer M, Schneider M D, Levine B (2005). Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 122(6): 927–939

    CAS  PubMed  Google Scholar 

  • Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A (2004). WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene, 23(58): 9314–9325

    CAS  PubMed  Google Scholar 

  • Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan R N, Gilpin C, Levine B (2007). Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell, 128(5): 931–946

    CAS  PubMed  Google Scholar 

  • Quan W, Kim H K, Moon E Y, Kim S S, Choi C S, Komatsu M, Jeong Y T, Lee M K, Kim K W, Kim M S, Lee M S (2012a). Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response. Endocrinology, 153(4): 1817–1826

    CAS  PubMed  Google Scholar 

  • Quan W, Lim Y M, Lee M S (2012b). Role of autophagy in diabetes and endoplasmic reticulum stress of pancreatic β-cells. Exp Mol Med, 44(2): 81–88

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raben N, Hill V, Shea L, Takikita S, Baum R, Mizushima N, Ralston E, Plotz P (2008). Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum Mol Genet, 17(24): 3897–3908

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rabinowitz J D, White E (2010). Autophagy and metabolism. Science, 330(6009): 1344–1348

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ravikumar B, Duden R, Rubinsztein D C (2002). Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet, 11(9): 1107–1117

    CAS  PubMed  Google Scholar 

  • Rodriguez A, Durán A, Selloum M, Champy M F, Diez-Guerra F J, Flores J M, Serrano M, Auwerx J, Diaz-Meco M T, Moscat J (2006). Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab, 3(3): 211–222

    CAS  PubMed  Google Scholar 

  • Ryter S W, Cloonan S M, Choi A M K (2013). Autophagy: a critical regulator of cellular metabolism and homeostasis. Mol Cells, 36(1): 7–16

    PubMed Central  CAS  PubMed  Google Scholar 

  • Santambrogio L, Cuervo A M (2011). Chasing the elusive mammalian microautophagy. Autophagy, 7(6): 652–654

    PubMed  Google Scholar 

  • Sengupta A, Molkentin J D, Yutzey K E (2009). FoxO transcription factors promote autophagy in cardiomyocytes. J Biol Chem, 284(41): 28319–28331

    PubMed Central  CAS  PubMed  Google Scholar 

  • Seok S, Fu T, Choi S E, Li Y, Zhu R, Kumar S, Sun X, Yoon G, Kang Y, Zhong W, Ma J, Kemper B, Kemper J K (2014). Transcriptional regulation of autophagy by an FXR-CREB axis. Nature, 516(7529): 108–111

    CAS  PubMed  Google Scholar 

  • Settembre C, De Cegli R, Mansueto G, Saha P K, Vetrini F, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch T J, Wollenberg A C, Di Bernardo D, Chan L, Irazoqui J E, Ballabio A (2013). TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol, 15(6): 647–658

    PubMed Central  CAS  PubMed  Google Scholar 

  • Settembre C, Di Malta C, Polito V A, Garcia Arencibia M, Vetrini F, Erdin S, Erdin S U, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein D C, Ballabio A (2011). TFEB links autophagy to lysosomal biogenesis. Science, 332(6036): 1429–1433

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shaid S, Brandts C H, Serve H, Dikic I (2013). Ubiquitination and selective autophagy. Cell Death Differ, 20(1): 21–30

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shang L, Wang X (2011). AMPK and mTOR coordinate the regulation of Ulk1 and mammalian autophagy initiation. Autophagy, 7(8): 924–926

    PubMed  Google Scholar 

  • Simonsen A, Birkeland H C, Gillooly D J, Mizushima N, Kuma A, Yoshimori T, Slagsvold T, Brech A, Stenmark H (2004). Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci, 117(Pt 18): 4239–4251

    CAS  PubMed  Google Scholar 

  • Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo A M, Czaja M J (2009a). Autophagy regulates lipid metabolism. Nature, 458(7242): 1131–1135

    PubMed Central  CAS  PubMed  Google Scholar 

  • Singh R, Xiang Y, Wang Y, Baikati K, Cuervo A M, Luu Y K, Tang Y, Pessin J E, Schwartz G J, Czaja M J (2009b). Autophagy regulates adipose mass and differentiation in mice. J Clin Invest, 119(11): 3329–3339

    PubMed Central  CAS  PubMed  Google Scholar 

  • Suzuki K, Kubota Y, Sekito T, Ohsumi Y (2007). Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells, 12(2): 209–218

    CAS  PubMed  Google Scholar 

  • Warr M R, Binnewies M, Flach J, Reynaud D, Garg T, Malhotra R, Debnath J, Passegué E (2013). FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature, 494(7437): 323–327

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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): 678–688

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wong E, Bejarano E, Rakshit M, Lee K, Hanson H H, Zaarur N, Phillips G R, Sherman M Y, Cuervo A M (2012). Molecular determinants of selective clearance of protein inclusions by autophagy. Nat Commun, 3: 1240

    PubMed Central  PubMed  Google Scholar 

  • Yang L, Li P, Fu S, Calay E S, Hotamisligil G S (2010). Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab, 11(6): 467–478

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang C, He Y, Okutsu M, Ong L C, Jin Y, Zheng L, Chow P, Yu S, Zhang M, Yan Z (2013). Autophagy is involved in adipogenic differentiation by repressesing proteasome-dependent PPARγ2 degradation. Am J Physiol Endocrinol Metab, 305(4): E530–E539

    CAS  PubMed  Google Scholar 

  • Zhang Y, Goldman S, Baerga R, Zhao Y, Komatsu M, Jin S (2009). Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci USA, 106(47): 19860–19865

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao J, Brault J J, Schild A, Cao P, Sandri M, Schiaffino S, Lecker S H, Goldberg A L (2007). FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab, 6(6): 472–483

    CAS  PubMed  Google Scholar 

  • Zheng Y T, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell J H (2009). The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol, 183(9): 5909–5916

    CAS  PubMed  Google Scholar 

  • Zhong Y, Wang Q J, Li X, Yan Y, Backer J M, Chait B T, Heintz N, Yue Z (2009). Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol, 11(4): 468–476

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhou G, Sebhat I K, Zhang B B (2009). AMPK activators—potential therapeutics for metabolic and other diseases. Acta Physiol (Oxf), 196(1): 175–190

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Altea Rocchi & Congcong He

Authors
  1. Altea Rocchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Congcong He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Congcong He.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rocchi, A., He, C. Emerging roles of autophagy in metabolism and metabolic disorders. Front. Biol. 10, 154–164 (2015). https://doi.org/10.1007/s11515-015-1354-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-015-1354-2

Keywords

Search

Navigation