Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 330 (6009): 1344-1348

Copyright © 2010 by the American Association for the Advancement of Science

Autophagy and Metabolism

Joshua D. Rabinowitz1,2, and Eileen White2,3,4

Abstract: Autophagy is a process of self-cannibalization. Cells capture their own cytoplasm and organelles and consume them in lysosomes. The resulting breakdown products are inputs to cellular metabolism, through which they are used to generate energy and to build new proteins and membranes. Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however—cancer cells exploit it to survive in nutrient-poor tumors.

1 Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, 241 Carl Icahn Laboratory, Washington Road, Princeton University, Princeton, NJ 08544, USA. E-mail: joshr{at}genomics.princeton.edu
2 Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
3 Department of Molecular Biology and Biochemistry, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA.
4 Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA. E-mail: whiteei{at}umdnj.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Autophagic Clearance of Mitochondria in the Kidney Copes with Metabolic Acidosis.
T. Namba, Y. Takabatake, T. Kimura, A. Takahashi, T. Yamamoto, J. Matsuda, H. Kitamura, F. Niimura, T. Matsusaka, H. Iwatani, et al. (2014)
J. Am. Soc. Nephrol.
   Abstract »
Mutational Landscape of the Essential Autophagy Gene BECN1 in Human Cancers.
S. V. Laddha, S. Ganesan, C. S. Chan, and E. White (2014)
Mol. Cancer Res. 12, 485-490
   Abstract »    Full Text »    PDF »
Lipid-enriched diet rescues lethality and slows down progression in a murine model of VCP-associated disease.
K. J. Llewellyn, A. Nalbandian, K.-M. Jung, C. Nguyen, A. Avanesian, T. Mozaffar, D. Piomelli, and V. E. Kimonis (2014)
Hum. Mol. Genet. 23, 1333-1344
   Abstract »    Full Text »    PDF »
The Undernourished Neonatal Mouse Metabolome Reveals Evidence of Liver and Biliary Dysfunction, Inflammation, and Oxidative Stress.
G. A. Preidis, M. A. Keaton, P. M. Campeau, B. C. Bessard, M. E. Conner, and P. J. Hotez (2014)
J. Nutr. 144, 273-281
   Abstract »    Full Text »    PDF »
Regulation of Akt Signaling by Sirtuins: Its Implication in Cardiac Hypertrophy and Aging.
V. B. Pillai, N. R. Sundaresan, and M. P. Gupta (2014)
Circ. Res. 114, 368-378
   Abstract »    Full Text »    PDF »
Lipid droplet autophagy in the yeast Saccharomyces cerevisiae.
T. van Zutphen, V. Todde, R. de Boer, M. Kreim, H. F. Hofbauer, H. Wolinski, M. Veenhuis, I. J. van der Klei, and S. D. Kohlwein (2014)
Mol. Biol. Cell 25, 290-301
   Abstract »    Full Text »    PDF »
{gamma}-Tocotrienol-induced autophagy in malignant mammary cancer cells.
R. V. Tiwari, P. Parajuli, and P. W. Sylvester (2014)
Experimental Biology and Medicine 239, 33-44
   Abstract »    Full Text »    PDF »
Evolutionary Analysis of Burkholderia pseudomallei Identifies Putative Novel Virulence Genes, Including a Microbial Regulator of Host Cell Autophagy.
A. P. Singh, S.-c. Lai, T. Nandi, H. H. Chua, W. F. Ooi, C. Ong, J. D. Boyce, B. Adler, R. J. Devenish, and P. Tan (2013)
J. Bacteriol. 195, 5487-5498
   Abstract »    Full Text »    PDF »
Skeletal Muscle-derived Myonectin Activates the Mammalian Target of Rapamycin (mTOR) Pathway to Suppress Autophagy in Liver.
M. M. Seldin, X. Lei, S. Y. Tan, K. P. Stanson, Z. Wei, and G. W. Wong (2013)
J. Biol. Chem. 288, 36073-36082
   Abstract »    Full Text »    PDF »
Dynamic association of the ULK1 complex with omegasomes during autophagy induction.
E. Karanasios, E. Stapleton, M. Manifava, T. Kaizuka, N. Mizushima, S. A. Walker, and N. T. Ktistakis (2013)
J. Cell Sci. 126, 5224-5238
   Abstract »    Full Text »    PDF »
Mechanism and Physiological Significance of Growth Factor-Related Autophagy.
T. Y. Li, S.-Y. Lin, and S.-C. Lin (2013)
Physiology 28, 423-431
   Abstract »    Full Text »    PDF »
Autophagy Sustains Mitochondrial Glutamine Metabolism and Growth of BrafV600E-Driven Lung Tumors.
A. M. Strohecker, J. Y. Guo, G. Karsli-Uzunbas, S. M. Price, G. J. Chen, R. Mathew, M. McMahon, and E. White (2013)
Cancer Discovery 3, 1272-1285
   Abstract »    Full Text »    PDF »
Exploiting the bad eating habits of Ras-driven cancers.
E. White (2013)
Genes & Dev. 27, 2065-2071
   Abstract »    Full Text »    PDF »
Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15.
C. Vantaggiato, C. Crimella, G. Airoldi, R. Polishchuk, S. Bonato, E. Brighina, M. Scarlato, O. Musumeci, A. Toscano, A. Martinuzzi, et al. (2013)
Brain 136, 3119-3139
   Abstract »    Full Text »    PDF »
Mitochondrial protein ATPase family, AAA domain containing 3A correlates with radioresistance in glioblastoma.
W.-C. You, S.-H. Chiou, C.-Y. Huang, S.-F. Chiang, C.-L. Yang, J. N. Sudhakar, T.-Y. Lin, I.-P. Chiang, C.-C. Shen, W.-Y. Cheng, et al. (2013)
Neuro Oncology 15, 1342-1352
   Abstract »    Full Text »    PDF »
Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita+/Ins2-derived {beta}-cells.
T. Mitchell, M. S. Johnson, X. Ouyang, B. K. Chacko, K. Mitra, X. Lei, Y. Gai, D. R. Moore, S. Barnes, J. Zhang, et al. (2013)
Am J Physiol Endocrinol Metab 305, E585-E599
   Abstract »    Full Text »    PDF »
Cardiac Metabolism in Heart Failure: Implications Beyond ATP Production.
T. Doenst, T. D. Nguyen, and E. D. Abel (2013)
Circ. Res. 113, 709-724
   Abstract »    Full Text »    PDF »
Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology.
Y. Cheng, X. Ren, W. N. Hait, and J.-M. Yang (2013)
Pharmacol. Rev. 65, 1162-1197
   Abstract »    Full Text »    PDF »
Autophagy: a potential therapeutic target in lung diseases.
K. Nakahira and A. M. K. Choi (2013)
Am J Physiol Lung Cell Mol Physiol 305, L93-L107
   Abstract »    Full Text »    PDF »
Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis.
J. Y. Guo, G. Karsli-Uzunbas, R. Mathew, S. C. Aisner, J. J. Kamphorst, A. M. Strohecker, G. Chen, S. Price, W. Lu, X. Teng, et al. (2013)
Genes & Dev. 27, 1447-1461
   Abstract »    Full Text »    PDF »
Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Phosphorylation by Protein Kinase C{delta} (PKC{delta}) Inhibits Mitochondria Elimination by Lysosomal-like Structures following Ischemia and Reoxygenation-induced Injury.
G. Yogalingam, S. Hwang, J. C. B. Ferreira, and D. Mochly-Rosen (2013)
J. Biol. Chem. 288, 18947-18960
   Abstract »    Full Text »    PDF »
Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway.
D.-M. Zhang, J.-S. Liu, L.-J. Deng, M.-F. Chen, A. Yiu, H.-H. Cao, H.-Y. Tian, K.-P. Fung, H. Kurihara, J.-X. Pan, et al. (2013)
Carcinogenesis 34, 1331-1342
   Abstract »    Full Text »    PDF »
Hypoxia-induced autophagy in endothelial cells: a double-edged sword in the progression of infantile haemangioma?.
G. Chen, W. Zhang, Y.-P. Li, J.-G. Ren, N. Xu, H. Liu, F.-Q. Wang, Z.-J. Sun, J. Jia, and Y.-F. Zhao (2013)
Cardiovasc Res 98, 437-448
   Abstract »    Full Text »    PDF »
The family that eats together stays together: new p53 family transcriptional targets in autophagy.
M. Napoli and E. R. Flores (2013)
Genes & Dev. 27, 971-974
   Abstract »    Full Text »    PDF »
TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3.
E. Boada-Romero, M. Letek, A. Fleischer, K. Pallauf, C. Ramon-Barros, and F. X. Pimentel-Muinos (2013)
EMBO J. 32, 566-582
   Abstract »    Full Text »    PDF »
Fat chance for longevity.
M. Kniazeva and M. Han (2013)
Genes & Dev. 27, 351-354
   Abstract »    Full Text »    PDF »
Chloroquine in Cancer Therapy: A Double-Edged Sword of Autophagy.
T. Kimura, Y. Takabatake, A. Takahashi, and Y. Isaka (2013)
Cancer Res. 73, 3-7
   Abstract »    Full Text »    PDF »
Key Roles for the Lipid Signaling Enzyme Phospholipase D1 in the Tumor Microenvironment During Tumor Angiogenesis and Metastasis.
Q. Chen, T. Hongu, T. Sato, Y. Zhang, W. Ali, J.-A. Cavallo, A. van der Velden, H. Tian, G. Di Paolo, B. Nieswandt, et al. (2012)
Science Signaling 5, ra79
   Abstract »    Full Text »    PDF »
Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition.
M. Cea, A. Cagnetta, M. Fulciniti, Y.-T. Tai, T. Hideshima, D. Chauhan, A. Roccaro, A. Sacco, T. Calimeri, F. Cottini, et al. (2012)
Blood 120, 3519-3529
   Abstract »    Full Text »    PDF »
Cell Death and Autophagy under Oxidative Stress: Roles of Poly(ADP-Ribose) Polymerases and Ca2+.
P. Wyrsch, C. Blenn, J. Bader, and F. R. Althaus (2012)
Mol. Cell. Biol. 32, 3541-3553
   Abstract »    Full Text »    PDF »
Autophagy Is a Protective Mechanism for Human Melanoma Cells under Acidic Stress.
M. L. Marino, P. Pellegrini, G. Di Lernia, M. Djavaheri-Mergny, S. Brnjic, X. Zhang, M. Hagg, S. Linder, S. Fais, P. Codogno, et al. (2012)
J. Biol. Chem. 287, 30664-30676
   Abstract »    Full Text »    PDF »
Conceptual Framework for Cutting the Pancreatic Cancer Fuel Supply.
A. Le, N. V. Rajeshkumar, A. Maitra, and C. V. Dang (2012)
Clin. Cancer Res. 18, 4285-4290
   Abstract »    Full Text »    PDF »
Central Role of Mitofusin 2 in Autophagosome-Lysosome Fusion in Cardiomyocytes.
T. Zhao, X. Huang, L. Han, X. Wang, H. Cheng, Y. Zhao, Q. Chen, J. Chen, H. Cheng, R. Xiao, et al. (2012)
J. Biol. Chem. 287, 23615-23625
   Abstract »    Full Text »    PDF »
Growth Inhibition by miR-519 via Multiple p21-Inducing Pathways.
K. Abdelmohsen, S. Srikantan, K. Tominaga, M.-J. Kang, Y. Yaniv, J. L. Martindale, X. Yang, S.-S. Park, K. G. Becker, M. Subramanian, et al. (2012)
Mol. Cell. Biol. 32, 2530-2548
   Abstract »    Full Text »    PDF »
Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1.
M. P. Ordonez, E. A. Roberts, C. U. Kidwell, S. H. Yuan, W. C. Plaisted, and L. S. B. Goldstein (2012)
Hum. Mol. Genet. 21, 2651-2662
   Abstract »    Full Text »    PDF »
Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to promote autophagy.
R. Sano, Y.-C. C. Hou, M. Hedvat, R. G. Correa, C.-W. Shu, M. Krajewska, P. W. Diaz, C. M. Tamble, G. Quarato, R. A. Gottlieb, et al. (2012)
Genes & Dev. 26, 1041-1054
   Abstract »    Full Text »    PDF »
Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy.
A. Orsi, M. Razi, H. C. Dooley, D. Robinson, A. E. Weston, L. M. Collinson, and S. A. Tooze (2012)
Mol. Biol. Cell 23, 1860-1873
   Abstract »    Full Text »    PDF »
Links between metabolism and cancer.
C. V. Dang (2012)
Genes & Dev. 26, 877-890
   Abstract »    Full Text »    PDF »
Regulation of selective autophagy onset by a Ypt/Rab GTPase module.
Z. Lipatova, N. Belogortseva, X. Q. Zhang, J. Kim, D. Taussig, and N. Segev (2012)
PNAS 109, 6981-6986
   Abstract »    Full Text »    PDF »
The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia.
R. Kang, T. Loux, D. Tang, N. E. Schapiro, P. Vernon, K. M. Livesey, A. Krasinskas, M. T. Lotze, and H. J. Zeh III (2012)
PNAS 109, 7031-7036
   Abstract »    Full Text »    PDF »
GSK3-TIP60-ULK1 Signaling Pathway Links Growth Factor Deprivation to Autophagy.
S.-Y. Lin, T. Y. Li, Q. Liu, C. Zhang, X. Li, Y. Chen, S.-M. Zhang, G. Lian, Q. Liu, K. Ruan, et al. (2012)
Science 336, 477-481
   Abstract »    Full Text »    PDF »
Atg7 Modulates p53 Activity to Regulate Cell Cycle and Survival During Metabolic Stress.
I. H. Lee, Y. Kawai, M. M. Fergusson, I. I. Rovira, A. J. R. Bishop, N. Motoyama, L. Cao, and T. Finkel (2012)
Science 336, 225-228
   Abstract »    Full Text »    PDF »
Cross talk between NADPH oxidase and autophagy in pulmonary artery endothelial cells with intrauterine persistent pulmonary hypertension.
R.-J. Teng, J. Du, S. Welak, T. Guan, A. Eis, Y. Shi, and G. G. Konduri (2012)
Am J Physiol Lung Cell Mol Physiol 302, L651-L663
   Abstract »    Full Text »    PDF »
Chronic Activation of mTOR Complex 1 Is Sufficient to Cause Hepatocellular Carcinoma in Mice.
S. Menon, J. L. Yecies, H. H. Zhang, J. J. Howell, J. Nicholatos, E. Harputlugil, R. T. Bronson, D. J. Kwiatkowski, and B. D. Manning (2012)
Science Signaling 5, ra24
   Abstract »    Full Text »    PDF »
Propeptide of Aminopeptidase 1 Protein Mediates Aggregation and Vesicle Formation in Cytoplasm-to-Vacuole Targeting Pathway.
M. Morales Quinones, J. T. Winston, and P. E. Stromhaug (2012)
J. Biol. Chem. 287, 10121-10133
   Abstract »    Full Text »    PDF »
A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB.
C. Settembre, R. Zoncu, D. L. Medina, F. Vetrini, S. Erdin, S. Erdin, T. Huynh, M. Ferron, G. Karsenty, M. C. Vellard, et al. (2012)
EMBO J. 31, 1095-1108
   Abstract »    Full Text »    PDF »
Mitochondrial dysfunction in ataxia-telangiectasia.
Y. A. Valentin-Vega, K. H. MacLean, J. Tait-Mulder, S. Milasta, M. Steeves, F. C. Dorsey, J. L. Cleveland, D. R. Green, and M. B. Kastan (2012)
Blood 119, 1490-1500
   Abstract »    Full Text »    PDF »
Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function.
N. Jaber, Z. Dou, J.-S. Chen, J. Catanzaro, Y.-P. Jiang, L. M. Ballou, E. Selinger, X. Ouyang, R. Z. Lin, J. Zhang, et al. (2012)
PNAS 109, 2003-2008
   Abstract »    Full Text »    PDF »
Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice.
V. Moresi, M. Carrer, C. E. Grueter, O. F. Rifki, J. M. Shelton, J. A. Richardson, R. Bassel-Duby, and E. N. Olson (2012)
PNAS 109, 1649-1654
   Abstract »    Full Text »    PDF »
Autophagy Driven by a Master Regulator of Hematopoiesis.
Y.-A. Kang, R. Sanalkumar, H. O'Geen, A. K. Linnemann, C.-J. Chang, E. E. Bouhassira, P. J. Farnham, S. Keles, and E. H. Bresnick (2012)
Mol. Cell. Biol. 32, 226-239
   Abstract »    Full Text »    PDF »
Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice.
M. Michaud, I. Martins, A. Q. Sukkurwala, S. Adjemian, Y. Ma, P. Pellegatti, S. Shen, O. Kepp, M. Scoazec, G. Mignot, et al. (2011)
Science 334, 1573-1577
   Abstract »    Full Text »    PDF »
Lysosomal Transmembrane Protein LAPTM4B Promotes Autophagy and Tolerance to Metabolic Stress in Cancer Cells.
Y. Li, Q. Zhang, R. Tian, Q. Wang, J. J. Zhao, J. D. Iglehart, Z. C. Wang, and A. L. Richardson (2011)
Cancer Res. 71, 7481-7489
   Abstract »    Full Text »    PDF »
Temporal orchestration of circadian autophagy rhythm by C/EBP{beta}.
D. Ma, S. Panda, and J. D. Lin (2011)
EMBO J. 30, 4642-4651
   Abstract »    Full Text »    PDF »
A Role for Rac3 GTPase in the Regulation of Autophagy.
W. L. Zhu, M. S. Hossain, D. Y. Guo, S. Liu, H. Tong, A. Khakpoor, P. J. Casey, and M. Wang (2011)
J. Biol. Chem. 286, 35291-35298
   Abstract »    Full Text »    PDF »
The dynamic nature of autophagy in cancer.
A. C. Kimmelman (2011)
Genes & Dev. 25, 1999-2010
   Abstract »    Full Text »    PDF »
The ATG1/ATG13 Protein Kinase Complex Is Both a Regulator and a Target of Autophagic Recycling in Arabidopsis.
A. Suttangkakul, F. Li, T. Chung, and R. D. Vierstra (2011)
PLANT CELL 23, 3761-3779
   Abstract »    Full Text »    PDF »
Targeted killing of a mammalian cell based upon its specialized metabolic state.
P. B. Alexander, J. Wang, and S. L. McKnight (2011)
PNAS 108, 15828-15833
   Abstract »    Full Text »    PDF »
Suppression of Autophagy by FIP200 Deletion Impairs DNA Damage Repair and Increases Cell Death upon Treatments with Anticancer Agents.
H. Bae and J.-L. Guan (2011)
Mol. Cancer Res. 9, 1232-1241
   Abstract »    Full Text »    PDF »
Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent.
A. Parkhitko, F. Myachina, T. A. Morrison, K. M. Hindi, N. Auricchio, M. Karbowniczek, J. J. Wu, T. Finkel, D. J. Kwiatkowski, J. J. Yu, et al. (2011)
PNAS 108, 12455-12460
   Abstract »    Full Text »    PDF »
Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis.
H. Wei, S. Wei, B. Gan, X. Peng, W. Zou, and J.-L. Guan (2011)
Genes & Dev. 25, 1510-1527
   Abstract »    Full Text »    PDF »
Ammonia-induced autophagy is independent of ULK1/ULK2 kinases.
H. Cheong, T. Lindsten, J. Wu, C. Lu, and C. B. Thompson (2011)
PNAS 108, 11121-11126
   Abstract »    Full Text »    PDF »
Role of Autophagy in Cancer Prevention.
H.-Y. Chen and E. White (2011)
Cancer Prevention Research 4, 973-983
   Abstract »    Full Text »    PDF »
Partners in Crime: Ubiquitin-Mediated Degradation and Autophagy.
(2011)
Science Signaling 4, jc4
Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation.
A. S. Rambold, B. Kostelecky, N. Elia, and J. Lippincott-Schwartz (2011)
PNAS 108, 10190-10195
   Abstract »    Full Text »    PDF »
TFEB Links Autophagy to Lysosomal Biogenesis.
C. Settembre, C. Di Malta, V. A. Polito, M. G. Arencibia, F. Vetrini, S. Erdin, S. U. Erdin, T. Huynh, D. Medina, P. Colella, et al. (2011)
Science 332, 1429-1433
   Abstract »    Full Text »    PDF »
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells.
Y. Inami, S. Waguri, A. Sakamoto, T. Kouno, K. Nakada, O. Hino, S. Watanabe, J. Ando, M. Iwadate, M. Yamamoto, et al. (2011)
J. Cell Biol. 193, 275-284
   Abstract »    Full Text »    PDF »
Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.
J. Y. Guo, H.-Y. Chen, R. Mathew, J. Fan, A. M. Strohecker, G. Karsli-Uzunbas, J. J. Kamphorst, G. Chen, J. M. S. Lemons, V. Karantza, et al. (2011)
Genes & Dev. 25, 460-470
   Abstract »    Full Text »    PDF »
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment.
R. K. Amaravadi, J. Lippincott-Schwartz, X.-M. Yin, W. A. Weiss, N. Takebe, W. Timmer, R. S. DiPaola, M. T. Lotze, and E. White (2011)
Clin. Cancer Res. 17, 654-666
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882