Skip to main content
SpringerLink
Log in

Autophagy in Cardiac Physiology and Pathology

  • Chapter
  • First Online:
Biochemistry of Apoptosis and Autophagy

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 18))

  • 840 Accesses

Abstract

Adult cardiomyocytes have only a limited capacity for regeneration, with intrinsic renewal rates of approximately 1% per year reported for humans and rodents. Individual cardiomyocytes are thus quite long-lived and must be able to continuously adapt to physiologic and pathophysiologic stresses. Stress adaptation often entails the renewal of intracellular constituents, as exemplified by the changes in enzymatic activity which accompanies shifts in oxygenation and metabolism, occurring during perinatal development; the modification in myofiber content in response to altered cardiac workload; and the renewal of proteins and organelles which takes place in response to reactive oxygen species-induced damage. Multiple proteolytic pathways have evolved to promote the efficient degradation of intracellular constituents, which is an essential step for their ultimate renewal. This chapter is focused on the role of the Autophagy in the heart. We begin with a description of types and molecular regulation of Autophagy, and then briefly summarize the importance of Autophagy in pathophysiologic regulation in other cell types. This is followed by a more detailed description of the role of Autophagy in cardiomyocytes during physiologic (i.e. perinatal development and physiologic hypertrophy), as well as pathophysiologic (i.e. cardiac atrophy, hypertrophy, proteinopathies and aging) conditions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Appelmans F, Wattiaux R, De Duve C (1955) Tissue fractionation studies. 5. The association of acid phosphatase with a special class of cytoplasmic granules in rat liver. Biochem J 3:438–445

    Article  Google Scholar 

  2. De Duve C, Pressman BC, Gianetto R et al (1955) Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J 4:604–617

    Article  Google Scholar 

  3. Novikoff AB, Beaufay H, De Duve C (1956) Electron microscopy of lysosomerich fractions from rat liver. J Biophys Biochem Cytol 4(Suppl):179–184

    Article  Google Scholar 

  4. Buechner, Letterer, Roulet (eds) (1955) Handbook of general physiology. Springer, Berlin-Goettingen-Heidelberg

    Google Scholar 

  5. Hruban Z, Spargo B, Swift H et al (1963) Focal cytoplasmic degradation. Am J Pathol 657–683

    Google Scholar 

  6. Ohsumi Y (1999) Molecular mechanism of autophagy in yeast, Saccharomyces cerevisiae. Philos Trans R Soc Lond B Biol Sci 1389:1577–1580; discussion 1580–1571

    Google Scholar 

  7. Soonpaa MH, Kim KK, Pajak L et al (1996) Cardiomyocyte DNA synthesis and binucleation during murine development. Am J Physiol 5(Pt 2):H2183-2189

    Google Scholar 

  8. Soonpaa MH, Rubart M, Field LJ (2013) Challenges measuring cardiomyocyte renewal. Biochim Biophys Acta 4:799–803

    Article  Google Scholar 

  9. Woodcock EA, Matkovich SJ (2005) Cardiomyocytes structure, function and associated pathologies. Int J Biochem Cell Biol 9:1746–1751

    Article  Google Scholar 

  10. Foglia MJ, Poss KD (2016) Building and re-building the heart by cardiomyocyte proliferation. Development 5:729–740

    Article  Google Scholar 

  11. O’Connell TD, Ishizaka S, Nakamura A et al (2003) The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse. J Clin Invest 11:1783–1791

    Article  Google Scholar 

  12. Maillet M, van Berlo JH, Molkentin JD (2013) Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 1:38–48

    Article  Google Scholar 

  13. Sutton MG, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 25:2981–2988

    Article  Google Scholar 

  14. Bui AL, Horwich TB, Fonarow GC (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 1:30–41

    Article  Google Scholar 

  15. Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 7:845–856

    Article  Google Scholar 

  16. Rubart M, Field LJ (2008) Stem cell differentiation: cardiac repair. Cells Tissues Organs 1–2:202–211

    Article  Google Scholar 

  17. Rubart M, Field LJ (2006) Cardiac regeneration: repopulating the heart. Annu Rev Physiol 29–49

    Google Scholar 

  18. Shimizu I, Minamino T (2016) Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 245–262

    Google Scholar 

  19. Willis MS, Bevilacqua A, Pulinilkunnil T et al (2014) The role of ubiquitin ligases in cardiac disease. J Mol Cell Cardiol 43–53

    Google Scholar 

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

    Article  Google Scholar 

  21. Bonaldo P, Sandri M (2013) Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 1:25–39

    Article  Google Scholar 

  22. Mizushima N (2007) Autophagy: process and function. Genes Dev 22:2861–2873

    Article  Google Scholar 

  23. Delorme-Axford E, Guimaraes RS, Reggiori F et al (2015) The yeast Saccharomyces cerevisiae: an overview of methods to study autophagy progression. Methods 3–12

    Google Scholar 

  24. Wesselborg S, Stork B (2015) Autophagy signal transduction by ATG proteins: from hierarchies to networks. Cell Mol Life Sci 24:4721–4757

    Article  Google Scholar 

  25. Arias E, Cuervo AM (2011) Chaperone-mediated autophagy in protein quality control. Curr Opin Cell Biol 2:184–189

    Article  Google Scholar 

  26. Kadowaki M, Karim MR, Carpi A et al (2006) Nutrient control of macroAutophagy in mammalian cells. Mol Aspects Med 5–6:426–443

    Article  Google Scholar 

  27. Talloczy Z, Jiang W, Virgin HWt et al (2002) Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A 1:190–195

    Google Scholar 

  28. Kanazawa T, Taneike I, Akaishi R et al (2004) Amino acids and insulin control autophagic proteolysis through different signaling pathways in relation to mTOR in isolated rat hepatocytes. J Biol Chem 9:8452–8459

    Article  Google Scholar 

  29. Pattingre S, Bauvy C, Codogno P (2003) Amino acids interfere with the ERK1/2-dependent control of macroAutophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells. J Biol Chem 19:16667–16674

    Article  Google Scholar 

  30. Jewell JL, Russell RC, Guan KL (2013) Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 3:133–139

    Article  Google Scholar 

  31. Kim YC, Guan KL (2015) mTOR: a pharmacologic target for autophagy regulation. J Clin Invest 1:25–32

    Article  Google Scholar 

  32. Schmelzle T, Beck T, Martin DE et al (2004) Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Mol Cell Biol 1:338–351

    Article  Google Scholar 

  33. Meijer AJ, Dubbelhuis PF (2004) Amino acid signalling and the integration of metabolism. Biochem Biophys Res Commun 2:397–403

    Article  Google Scholar 

  34. Meijer AJ, Codogno P (2007) AMP-activated protein kinase and autophagy. Autophagy 3:238–240

    Google Scholar 

  35. Hoyer-Hansen M, Bastholm L, Szyniarowski P et al (2007) Control of macroAutophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 2:193–205

    Article  Google Scholar 

  36. Mammucari C, Milan G, Romanello V et al (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6:458–471

    Article  CAS  PubMed  Google Scholar 

  37. Zhao J, Brault JJ, Schild A et al (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6:472–483

    Article  CAS  PubMed  Google Scholar 

  38. Lee WS, Yoo WH, Chae HJ (2015) ER Stress and autophagy. Curr Mol Med 8:735–745

    Article  Google Scholar 

  39. Glembotski CC (2008) The role of the unfolded protein response in the heart. J Mol Cell Cardiol 3:453–459

    Article  Google Scholar 

  40. B’Chir W, Maurin AC, Carraro V et al (2013) The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res 16:7683–7699

    Article  Google Scholar 

  41. Jiang Q, Li F, Shi K et al (2014) Involvement of p38 in signal switching from autophagy to apoptosis via the PERK/eIF2alpha/ATF4 axis in selenite-treated NB4 cells. Cell Death Dis e1270

    Google Scholar 

  42. Zaglia T, Milan G, Ruhs A et al (2014) Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. J Clin Invest 6:2410–2424

    Article  Google Scholar 

  43. Korolchuk VI, Menzies FM, Rubinsztein DC (2010) Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems. FEBS Lett 7:1393–1398

    Article  Google Scholar 

  44. Su H, Wang X (2011) p62 Stages an interplay between the ubiquitin-proteasome system and autophagy in the heart of defense against proteotoxic stress. Trends Cardiovasc Med 8:224–228

    Article  Google Scholar 

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

    Google Scholar 

  46. Kuma A, Hatano M, Matsui M et al (2004) The role of autophagy during the early neonatal starvation period. Nature 7020:1032–1036

    Article  Google Scholar 

  47. Deretic V (2005) Autophagy in innate and adaptive immunity. Trends Immunol 10:523–528

    Article  Google Scholar 

  48. Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 10:767–777

    Article  Google Scholar 

  49. Madeo F, Zimmermann A, Maiuri MC et al (2015) Essential role for autophagy in life span extension. J Clin Invest 1:85–93

    Article  Google Scholar 

  50. Simonsen A, Cumming RC, Brech A et al (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 2:176–184

    Article  Google Scholar 

  51. Hars ES, Qi H, Ryazanov AG et al (2007) Autophagy regulates ageing in C. elegans. Autophagy 2:93–95

    Article  Google Scholar 

  52. Komatsu M, Waguri S, Chiba T et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 7095:880–884

    Article  Google Scholar 

  53. Ogata M, Hino S, Saito A et al (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 24:9220–9231

    Article  Google Scholar 

  54. Lee JA, Gao FB (2008) Roles of ESCRT in autophagy-associated neurodegeneration. Autophagy 2:230–232

    Article  Google Scholar 

  55. Lee JA, Beigneux A, Ahmad ST et al (2007) ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol 18:1561–1567

    Article  Google Scholar 

  56. Ravikumar B, Vacher C, Berger Z et al (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 6:585–595

    Article  Google Scholar 

  57. Sarkar S, Perlstein EO, Imarisio S et al (2007) Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 6:331–338

    Article  Google Scholar 

  58. Lacoste-Collin L, Garcia V, Uro-Coste E et al (2002) Danon’s disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation. Neuromuscul Disord 9:882–885

    Article  Google Scholar 

  59. Tanaka Y, Guhde G, Suter A et al (2000) Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 6798:902–906

    Article  Google Scholar 

  60. Mathew R, Kongara S, Beaudoin B et al (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 11:1367–1381

    Article  Google Scholar 

  61. Dorsey FC, Steeves MA, Prater SM et al (2009) Monitoring the autophagy pathway in cancer. Methods Enzymol 251–271

    Google Scholar 

  62. Maiuri MC, Zalckvar E, Kimchi A et al (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 9:741–752

    Article  Google Scholar 

  63. Kenific CM, Debnath J (2015) Cellular and metabolic functions for autophagy in cancer cells. Trends Cell Biol 1:37–45

    Article  Google Scholar 

  64. Kroemer G, Galluzzi L, Vandenabeele P et al (2009) Classification of cell death: recommendations of the nomenclature Committee on Cell Death 2009. Cell Death Differ 1:3–11

    Article  Google Scholar 

  65. Lockshin RA, Zakeri Z (2001) Programmed cell death and apoptosis: origins of the theory. Nat Rev Mol Cell Biol 7:545–550

    Article  Google Scholar 

  66. Nelson C, Baehrecke EH (2014) Autophagy and cell death in the fly. Methods Enzymol 181–199.

    Google Scholar 

  67. Denton D, Xu T, Kumar S (2015) Autophagy as a pro-death pathway. Immunol Cell Biol 1:35–42

    Article  Google Scholar 

  68. Chatterjee T, Muhkopadhyay A, Khan KA et al (1998) Comparative mutagenic and genotoxic effects of three antimalarial drugs, chloroquine, primaquine and amodiaquine. Mutagenesis 6:619–624

    Article  Google Scholar 

  69. McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 10:737–747

    Article  Google Scholar 

  70. Yousefi S, Perozzo R, Schmid I et al (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 10:1124–1132

    Article  Google Scholar 

  71. Zhu H, Tannous P, Johnstone JL et al (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 7:1782–1793

    Article  Google Scholar 

  72. Marino G, Niso-Santano M, Baehrecke EH et al (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 2:81–94

    Article  Google Scholar 

  73. Amir M, Zhao E, Fontana L et al (2013) Inhibition of hepatocyte autophagy increases tumor necrosis factor-dependent liver injury by promoting caspase-8 activation. Cell Death Differ 7:878–887

    Article  Google Scholar 

  74. Sandilands E, Serrels B, Wilkinson S et al (2012) Src-dependent autophagic degradation of Ret in FAK-signalling-defective cancer cells. EMBO Rep 8:733–740

    Article  Google Scholar 

  75. Kim I, Lemasters JJ (2011) Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation. Am J Physiol Cell Physiol 2:C308-317

    Article  Google Scholar 

  76. Oral O, Oz-Arslan D, Itah Z et al (2012) Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death. Apoptosis 8:810–820

    Article  Google Scholar 

  77. Luo S, Rubinsztein DC (2010) Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL. Cell Death Differ 2:268–277

    Article  Google Scholar 

  78. Wirawan E, Vande Walle L, Kersse K et al (2010) Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis e18

    Google Scholar 

  79. Komatsu M, Waguri S, Ueno T et al (2005) Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 3:425–434

    Article  Google Scholar 

  80. Viragh S, Szabo E, Challice CE (1982) Glycogen-containing lysosomes and glycogen loss in the cardiocytes of embryonic and neonatal mice. Adv Myocardiol 553–561

    Google Scholar 

  81. Saugstad OD (2005) Oxidative stress in the newborn—a 30-year perspective. Biol Neonate 3:228–236

    Article  Google Scholar 

  82. Scherz-Shouval R, Shvets E, Fass E et al (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. Embo j 7:1749–1760

    Article  Google Scholar 

  83. Scherz-Shouval R, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 9:422–427

    Article  Google Scholar 

  84. Nishino I, Fu J, Tanji K et al (2000) Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 6798:906–910

    Article  Google Scholar 

  85. Pattison JS, Robbins J (2011) Autophagy and proteotoxicity in cardiomyocytes. Autophagy 10:1259–1260

    Article  Google Scholar 

  86. Nakai A, Yamaguchi O, Takeda T et al (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 5:619–624

    Article  Google Scholar 

  87. Samarel AM, Parmacek MS, Magid NM et al (1987) Protein synthesis and degradation during starvation-induced cardiac atrophy in rabbits. Circ Res 6:933–941

    Article  Google Scholar 

  88. Kolar F, MacNaughton C, Papousek F et al (1993) Systolic mechanical performance of heterotopically transplanted hearts in rats treated with cyclosporin. Cardiovasc Res 7:1244–1247

    Article  Google Scholar 

  89. Perhonen MA, Franco F, Lane LD et al (2001) Cardiac atrophy after bed rest and spaceflight. J Appl Physiol 2:645–653

    Article  Google Scholar 

  90. Crie JS, Sanford CF, Wildenthal K (1980) Influence of starvation and refeeding on cardiac protein degradation in rats. J Nutr 1:22–27

    Article  Google Scholar 

  91. Burch GE, Phillips JH, Ansari A (1968) The cachetic heart. A clinico-pathologic, electrocardiographic and roentgenographic entity. Dis Chest 5:403–409

    Article  Google Scholar 

  92. Zhou X, Wang JL, Lu J et al (2010) Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 4:531–543

    Article  Google Scholar 

  93. Cosper PF, Leinwand LA (2011) Cancer causes cardiac atrophy and Autophagy in a sexually dimorphic manner. Cancer Res 5:1710–1720

    Article  Google Scholar 

  94. Toledo M, Busquets S, Penna F et al (2016) Complete reversal of muscle wasting in experimental cancer cachexia: additive effects of activin type II receptor inhibition and beta-2 agonist. Int J Cancer 8:2021–2029

    Article  Google Scholar 

  95. Mettauer B, Rouleau JL, Burgess JH (1985) Detrimental arrhythmogenic and sustained beneficial hemodynamic effects of oral salbutamol in patients with chronic congestive heart failure. Am Heart J 4:840–847

    Article  Google Scholar 

  96. Molenaar P, Chen L, Parsonage WA (2006) Cardiac implications for the use of beta2-adrenoceptor agonists for the management of muscle wasting. Br J Pharmacol 6:583–586

    Article  Google Scholar 

  97. Goldstein MA, Edwards RJ, Schroeter JP (1992) Cardiac morphology after conditions of microgravity during COSMOS 2044. J Appl Physiol (2 Suppl):94s–100s

    Google Scholar 

  98. Kadner A, Chen RH, Adams DH (2000) Heterotopic heart transplantation: experimental development and clinical experience. Eur J Cardiothorac Surg 4:474–481

    Article  Google Scholar 

  99. Razeghi P, Volpini KC, Wang ME et al (2007) Mechanical unloading of the heart activates the calpain system. J Mol Cell Cardiol 2:449–452

    Article  Google Scholar 

  100. Kassiotis C, Ballal K, Wellnitz K et al (2009) Markers of Autophagy are downregulated in failing human heart after mechanical unloading. Circulation 11(Suppl):S191-197

    Google Scholar 

  101. Zaglia T, Milan G, Franzoso M et al (2013) Cardiac sympathetic neurons provide trophic signal to the heart via beta2-adrenoceptor-dependent regulation of proteolysis. Cardiovasc Res 2:240–250

    Article  Google Scholar 

  102. de Lange P, Moreno M, Silvestri E et al (2007) Fuel economy in food-deprived skeletal muscle: signaling pathways and regulatory mechanisms. Faseb j 13:3431–3441

    Article  Google Scholar 

  103. Wu J, Ruas JL, Estall JL et al (2011) The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1alpha/ATF6alpha complex. Cell Metab 2:160–169

    Article  Google Scholar 

  104. Sahlin K, Shabalina IG, Mattsson CM et al (2010) Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle. J Appl Physiol 4:780–787

    Article  Google Scholar 

  105. Jamart C, Benoit N, Raymackers JM et al (2012) Autophagy-related and autophagy-regulatory genes are induced in human muscle after ultraendurance exercise. Eur J Appl Physiol 8:3173–3177

    Article  Google Scholar 

  106. He C, Bassik MC, Moresi V et al (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 7382:511–515

    Article  Google Scholar 

  107. Rothermel BA, Hill JA (2007) Myocyte autophagy in heart disease: friend or foe? Autophagy 6:632–634

    Article  Google Scholar 

  108. Rothermel BA, Hill JA (2008) Autophagy in load-induced heart disease. Circ Res 12:1363–1369

    Article  Google Scholar 

  109. Tannous P, Zhu H, Nemchenko A et al (2008) Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy. Circulation 24:3070–3078

    Article  Google Scholar 

  110. Wang C, Wang X (2015) The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity. Biochim Biophys Acta 2:188–194

    Article  Google Scholar 

  111. Su H, Li J, Zhang H et al (2015) COP9 signalosome controls the degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity. Circ Res 11:956–966

    Article  Google Scholar 

  112. Willis MS, Patterson C (2013) Proteotoxicity and cardiac dysfunction–Alzheimer’s disease of the heart? N Engl J Med 5:455–464

    Article  Google Scholar 

  113. Bennardini F, Wrzosek A, Chiesi M (1992) Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments. Circ Res 2:288–294

    Article  Google Scholar 

  114. Nicholl ID, Quinlan RA (1994) Chaperone activity of alpha-crystallins modulates intermediate filament assembly. Embo J 4:945–953

    Article  Google Scholar 

  115. Wang K, Spector A (1996) alpha-crystallin stabilizes actin filaments and prevents cytochalasin-induced depolymerization in a phosphorylation-dependent manner. Eur J Biochem 1:56–66

    Article  Google Scholar 

  116. Wang X, Osinska H, Klevitsky R et al (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res 1:84–91

    Article  Google Scholar 

  117. Wang X, Osinska H, Dorn GW 2nd et al (2001) Mouse model of desmin-related cardiomyopathy. Circulation 19:2402–2407

    Article  Google Scholar 

  118. Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science 5521:1552–1555

    Article  Google Scholar 

  119. Tannous P, Zhu H, Johnstone JL et al (2008) Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A 28:9745–9750

    Article  Google Scholar 

  120. Bhuiyan MS, Pattison JS, Osinska H et al (2013) Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest 12:5284–5297

    Article  Google Scholar 

  121. Sanbe A, Daicho T, Mizutani R et al (2009) Protective effect of geranylgeranylacetone via enhancement of HSPB8 induction in desmin-related cardiomyopathy. PLoS One 4:e5351

    Google Scholar 

  122. Shirakabe A, Ikeda Y, Sciarretta S et al (2016) Aging and autophagy in the heart. Circ Res 10:1563–1576

    Article  Google Scholar 

  123. Nakayama H, Nishida K, Otsu K (2016) Macromolecular degradation systems and cardiovascular aging. Circ Res 10:1577–1592

    Article  Google Scholar 

  124. Linton PJ, Gurney M, Sengstock D et al (2015) This old heart: cardiac aging and autophagy. J Mol Cell Cardiol 44–54

    Google Scholar 

  125. Terman A, Kurz T, Navratil M et al (2010) Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid Redox Signal 4:503–535

    Article  Google Scholar 

  126. Li L, Chen Y, Gibson SB (2013) Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cell Signal 1:50–65

    Article  CAS  Google Scholar 

  127. Taneike M, Yamaguchi O, Nakai A et al (2010) Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy 5:600–606

    Article  Google Scholar 

  128. Zheng K, Li Y, Wang S et al (2016) Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint. Autophagy 9:1593–1613

    Article  Google Scholar 

  129. Jaishy B, Zhang Q, Chung HS et al (2015) Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity. J Lipid Res 3:546–561

    Article  Google Scholar 

  130. Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 6:542–545

    Article  Google Scholar 

  131. Harrison DE, Strong R, Sharp ZD et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 7253:392–395

    Article  Google Scholar 

  132. Lee IH, Cao L, Mostoslavsky R et al (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A 9:3374–3379

    Article  Google Scholar 

  133. Matsushima S, Sadoshima J (2015) The role of sirtuins in cardiac disease. Am J Physiol Heart Circ Physiol 9:H1375-1389

    Article  Google Scholar 

  134. Alvers AL, Wood MS, Hu D et al (2009) Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy 6:847–849

    Article  Google Scholar 

  135. Speakman JR, Mitchell SE (2011) Caloric restriction. Mol Aspects Med 3:159–221

    Article  Google Scholar 

  136. Sujkowski A, Bazzell B, Carpenter K et al (2015) Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms. Aging (Albany NY) 8:535–552

    Article  Google Scholar 

  137. Chung E, Leinwand LA (2014) Pregnancy as a cardiac stress model. Cardiovasc Res 4:561–570

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to Marco Mongillo (University of Padova) for critical reading and discussion, and Nicola Pianca, Ph.D. (University of Padova) for critical reading and technical assistance.

Author information

Authors and Affiliations

  1. Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, via Giustiniani 2, 35128,, Padova, Italy

    Tania Zaglia

  2. Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35122,, Padova, Italy

    Tania Zaglia

  3. Veneto Institute of Molecular Medicine, Via Orus 2, 35129,, Padova, Italy

    Tania Zaglia

  4. The Krannert Institute of Cardiology and the Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA

    Loren J. Field

Authors
  1. Tania Zaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loren J. Field
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tania Zaglia .

Editor information

Editors and Affiliations

  1. University of Manitoba, Winnipeg, MB, Canada

    Lorrie A. Kirshenbaum

Ethics declarations

Conflict of Interest

Nothing to declare.

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zaglia, T., Field, L.J. (2022). Autophagy in Cardiac Physiology and Pathology. In: Kirshenbaum, L.A. (eds) Biochemistry of Apoptosis and Autophagy. Advances in Biochemistry in Health and Disease, vol 18. Springer, Cham. https://doi.org/10.1007/978-3-030-78799-8_4

Download citation

Publish with us

Policies and ethics

Search

Navigation