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Autophagy and Energy Metabolism

  • Jie Yang
  • Ruimin Zhou
  • Zhenyi MaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1206)

Abstract

Autophagy is a lysosome-dependent catabolic process. Both extra- and intra-cellular components are engulfed in autophagic vacuoles and degraded to simple molecules, such as monosaccharides, fatty acids and amino acids. Then, these molecules can be further used to produce ATP through catabolic reactions and/or provide building blocks for the synthesis of essential proteins. Therefore, we consider autophagy a critical and fine-tuned process in maintaining energy homeostasis. The complicated relationships between autophagy and energy metabolism have raised broad interest and have been extensively studied. In this chapter, we summarize the relationships enabling autophagy to control or modulate energy metabolism and allowing metabolic pathways to regulate autophagy. Specifically, we review the correlations between autophagy and energy homeostasis in terms of oxidative phosphorylation, reactive oxygen species in mitochondria, glycolysis, metabolism of glycogen and protein, and so on. An understanding of the role of autophagy in energy homeostasis could help us better appreciate how autophagy determines cell fate under stressful conditions or pathological processes.

Keywords

ATP Amino acid Autophagy Carbohydrate Energy Glycogen 

Abbreviations

2-DG

2-deoxy-D-glucose

3-MA

3-methyladenine

4E-BP1

Eukaryotic initiation factor 4E binding protein 1

α-KG

α-ketoglutaric acid

ABCC1

ATP-binding cassette C1

ADI

Arginine deiminase

AICAR

5-aminoimidazole-4-carboxamide ribonucleoside

AMBRA

Activating molecule in Beclin1-regulated autophagy

AMPK

Adenosine 5′-monophosphate (AMP)-activated protein kinase

ASS

Argininosuccinate synthetase

ATF4

Activating transcription factor 4

ATG

Autophagy-related gene

ATP

Adenosine triphosphate

BNIP3

Bcl2/adenovirus E1B 19-kDa protein-interacting protein 3

CBM

Carbohydrate-binding module

CMA

Chaperone-mediated autophagy

DAPK-1

Death-associated protein kinase 1

eIF

Eukaryotic initiation factor

EGLN

Egl-9 family hypoxia-inducible factor

F2,6BP

Fructose-2,6-bisphosphate

FCCP

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone

FOXO

Forkhead box O

G6P

Glucose-6-phosphate

G6PC

Glucose-6-phosphatase α

G6PD

Glucose-6-phosphate dehydrogenase

GAA

Lysosomal acid α-glucosidase

GABARAPL1

Γ-aminobutyric acid receptor-associated protein-like 1

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GCL

Γ-glutamate cysteine ligase

GILT

Interferon-γ-inducible lysosomal thiol reductase

GLS

Glutaminase

GLUD1

Glutamate Dehydrogenase 1

GSH

Glutathione, γ-L-glutamyl-L-cysteinyl-glycine (reduced)

GSK3

Glycogen synthase kinase 3

GSSH

Glutathione, γ-L-glutamyl-L-cysteinyl-glycine (oxidized)

HIF

Hypoxia-inducible factor

HK

Hexokinase

HSC70

Heat shock cognate protein 70

ICD

Immunogenic cell death

LAMP2A

Lysosome-associated membrane protein type 2A

LC3

Microtubule-associated protein 1 light chain 3 (MAP1LC3)

LDHB

Lactate dehydrogenase B

MPC

Mitochondrial pyruvate carrier protein

mTOR

Mammalian target of rapamycin

NADH/NAD+

Nicotinamide adenine dinucleotide

NADPH

Nicotinamide adenine dinucleotide phosphate

NOX

NADPH oxidase

PARP1

Poly(ADP-ribose) polymerase 1

PFKFB4

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4

PI3K

Phosphatidylinositol 3-kinase

PI3P

Phosphatidylinositol-3-phosphate

PIP3

Phosphatidylinositol 3,4,5-trisphosphate

PK

Pyruvate kinase

PKM2

Pyruvate kinase M2 isoform

PKA

Protein kinase A

PKB

Protein kinase B, also known as Akt

PPP

Pentose phosphate pathway

PRODH/POX

Proline dehydrogenase/oxidase

Raptor

Regulatory-associated protein of mTOR

Rheb

Ras homolog enriched in brain

ROS

Reactive oxygen species

SIRT

Sirtuin

SLC1A5

Solute carrier family 1 (neutral amino acid transporter) member 5

SNAREs

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors

SOD

Superoxide dismutase

SQSTM1/p62

Sequestosome 1/p62

Stbd1

Starch-binding domain-containing protein 1

TFEB

Transcription factor EB

TIGAR

TP53-induced glycolysis and apoptosis regulator

TRAF6

TNF receptor-associated factor 6

TSC1/2

Tuberous sclerosis 1/2 protein

ULK1

Unc-51-like autophagy activating kinase 1

v-ATPase

Vacuolar H+-adenosine triphosphatase ATPase

Vps34

Vacuole protein sorting 34 (class III phosphatidylinositol 3-kinase)

References

  1. Bloy N, Garcia P, Laumont CM, Pitt JM, Sistigu A, Stoll G, Yamazaki T, Bonneil E, Buque A, Humeau J, Drijfhout JW, Meurice G, Walter S, Fritsche J, Weinschenk T, Rammensee HG, Melief C, Thibault P, Perreault C, Pol J, Zitvogel L, Senovilla L, Kroemer G (2017) Immunogenic stress and death of cancer cells: contribution of antigenicity vs adjuvanticity to immunosurveillance. Immunol Rev 280(1):165–174.  https://doi.org/10.1111/imr.12582CrossRefPubMedGoogle Scholar
  2. Brisson L, Bański P, Sboarina M, Dethier C, Danhier P, Fontenille M-J, Van Hée Vincent F, Vazeille T, Tardy M, Falces J, Bouzin C, Porporato Paolo E, Frédérick R, Michiels C, Copetti T, Sonveaux P (2016) Lactate dehydrogenase B controls lysosome activity and autophagy in cancer. Cancer Cell 30(3):418–431.  https://doi.org/10.1016/j.ccell.2016.08.005CrossRefPubMedGoogle Scholar
  3. Carroll B, Korolchuk VI, Sarkar S (2015) Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis. Amino Acids 47(10):2065–2088.  https://doi.org/10.1007/s00726-014-1775-2CrossRefPubMedGoogle Scholar
  4. Dodson M, Darley-Usmar V, Zhang J (2013) Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med 63:207–221.  https://doi.org/10.1016/j.freeradbiomed.2013.05.014CrossRefPubMedPubMedCentralGoogle Scholar
  5. Farah BL, Landau DJ, Sinha RA, Brooks ED, Wu Y, Fung SYS, Tanaka T, Hirayama M, Bay BH, Koeberl DD, Yen PM (2016) Induction of autophagy improves hepatic lipid metabolism in glucose-6-phosphatase deficiency. J Hepatol 64(2):370–379.  https://doi.org/10.1016/j.jhep.2015.10.008CrossRefPubMedGoogle Scholar
  6. Filomeni G, De Zio D, Cecconi F (2015) Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ 22(3):377–388.  https://doi.org/10.1038/cdd.2014.150CrossRefPubMedGoogle Scholar
  7. Galluzzi L, Pietrocola F, Levine B, Kroemer G (2014) Metabolic control of autophagy. Cell 159(6):1263–1276.  https://doi.org/10.1016/j.cell.2014.11.006CrossRefPubMedPubMedCentralGoogle Scholar
  8. Ha J, Guan K-L, Kim J (2015) AMPK and autophagy in glucose/glycogen metabolism. Mol Aspects Med 46:46–62.  https://doi.org/10.1016/j.mam.2015.08.002CrossRefPubMedGoogle Scholar
  9. Jiao L, Zhang HL, Li DD, Yang KL, Tang J, Li X, Ji J, Yu Y, Wu RY, Ravichandran S, Liu JJ, Feng GK, Chen MS, Zeng YX, Deng R, Zhu XF (2018) Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2). Autophagy 14(4):671–684.  https://doi.org/10.1080/15548627.2017.1381804CrossRefPubMedGoogle Scholar
  10. Kaur J, Debnath J (2015) Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 16(8):461–472.  https://doi.org/10.1038/nrm4024CrossRefPubMedGoogle Scholar
  11. Khaminets A, Behl C, Dikic I (2016) Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol 26(1):6–16.  https://doi.org/10.1016/j.tcb.2015.08.010CrossRefPubMedGoogle Scholar
  12. Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441(2):523–540.  https://doi.org/10.1042/BJ20111451CrossRefPubMedGoogle Scholar
  13. Lindqvist LM, Tandoc K, Topisirovic I, Furic L (2018) Cross-talk between protein synthesis, energy metabolism and autophagy in cancer. Curr Opin Genet Dev 48:104–111.  https://doi.org/10.1016/j.gde.2017.11.003CrossRefPubMedGoogle Scholar
  14. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, Wang G, Huang Y, Xiong Y, Guan K-L, Lei Q-Y (2011) Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 42(6):719–730.  https://doi.org/10.1016/j.molcel.2011.04.025CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ma X, Jin M, Cai Y, Xia H, Long K, Liu J, Yu Q, Yuan J (2011) Mitochondrial electron transport chain complex III is required for antimycin A to inhibit autophagy. Chem Biol 18(11):1474–1481.  https://doi.org/10.1016/j.chembiol.2011.08.009CrossRefPubMedPubMedCentralGoogle Scholar
  16. Marchand B, Arsenault D, Raymond-Fleury A, Boisvert FM, Boucher MJ (2015) Glycogen synthase kinase-3 (GSK3) inhibition induces prosurvival autophagic signals in human pancreatic cancer cells. J Biol Chem 290(9):5592–5605.  https://doi.org/10.1074/jbc.M114.616714CrossRefPubMedPubMedCentralGoogle Scholar
  17. Mariño G, Pietrocola F, Eisenberg T, Kong Y, Malik Shoaib A, Andryushkova A, Schroeder S, Pendl T, Harger A, Niso-Santano M, Zamzami N, Scoazec M, Durand S, Enot David P, Fernández Álvaro F, Martins I, Kepp O, Senovilla L, Bauvy C, Morselli E, Vacchelli E, Bennetzen M, Magnes C, Sinner F, Pieber T, López-Otín C, Maiuri Maria C, Codogno P, Andersen Jens S, Hill Joseph A, Madeo F, Kroemer G (2014) Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell 53(5):710–725.  https://doi.org/10.1016/j.molcel.2014.01.016CrossRefPubMedGoogle Scholar
  18. Prakasam G, Singh RK, Iqbal MA, Saini SK, Tiku AB, Bamezai RNK (2017) Pyruvate kinase M knockdown-induced signaling via AMP-activated protein kinase promotes mitochondrial biogenesis, autophagy, and cancer cell survival. J Biol Chem 292(37):15561–15576.  https://doi.org/10.1074/jbc.M117.791343CrossRefPubMedPubMedCentralGoogle Scholar
  19. Quansah E, Peelaerts W, Langston JW, Simon DK, Colca J, Brundin P (2018) Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. Molecular Neurodegeneration 13(1):28–28.  https://doi.org/10.1186/s13024-018-0260-xCrossRefPubMedPubMedCentralGoogle Scholar
  20. Rabinowitz JD, White E (2010) Autophagy and metabolism. Science 330(6009):1344–1348.  https://doi.org/10.1126/science.1193497CrossRefPubMedPubMedCentralGoogle Scholar
  21. Roberts DJ, Tan-Sah VP, Ding EY, Smith JM, Miyamoto S (2014) Hexokinase-II positively regulates glucose starvation-induced autophagy through TORC1 inhibition. Mol Cell 53(4):521–533.  https://doi.org/10.1016/j.molcel.2013.12.019CrossRefPubMedPubMedCentralGoogle Scholar
  22. Robke L, Futamura Y, Konstantinidis G, Wilke J, Aono H, Mahmoud Z, Watanabe N, Wu YW, Osada H, Laraia L, Waldmann H (2018) Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I. Chem Sci 9(11):3014–3022.  https://doi.org/10.1039/c7sc05040bCrossRefPubMedPubMedCentralGoogle Scholar
  23. Strohecker AM, Joshi S, Possemato R, Abraham RT, Sabatini DM, White E (2015) Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel autophagy regulator by high content shRNA screening. Oncogene 34(45):5662–5676.  https://doi.org/10.1038/onc.2015.23CrossRefPubMedPubMedCentralGoogle Scholar
  24. Tan HWS, Sim AYL, Long YC (2017) Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation. Nat Commun 8(1):338.  https://doi.org/10.1038/s41467-017-00369-yCrossRefPubMedPubMedCentralGoogle Scholar
  25. Yan S, Wei X, Xu S, Sun H, Wang W, Liu L, Jiang X, Zhang Y, Che Y (2017) 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 spatially mediates autophagy through the AMPK signaling pathway. Oncotarget 8(46):80909–80922.  https://doi.org/10.18632/oncotarget.20757CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

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