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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
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
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.12582
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.2016.08.005
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/s00726-014-1775-2
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.2013.05.014
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.2015.10.008
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.2014.150
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.2014.11.006
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.2015.08.002
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/10.1080/15548627.2017.1381804
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/nrm4024
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.2015.08.010
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/BJ20111451
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.2017.11.003
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.2011.04.025
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.2011.08.009
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.M114.616714
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.2014.01.016
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.M117.791343
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-x
Rabinowitz JD, White E (2010) Autophagy and metabolism. Science 330(6009):1344–1348. https://doi.org/10.1126/science.1193497
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.2013.12.019
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/c7sc05040b
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.2015.23
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-y
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.20757
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Science Press and Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Yang, J., Zhou, R., Ma, Z. (2019). Autophagy and Energy Metabolism. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_16
Download citation
DOI: https://doi.org/10.1007/978-981-15-0602-4_16
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-0601-7
Online ISBN: 978-981-15-0602-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)