Autophagy and Metabolism
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 Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones.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.
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References
1
Kuma A., Mizushima N., Semin. Cell Dev. Biol. 21, 683 (2010).
2
Funderburk S. F., Wang Q. J., Yue Z., The Beclin 1-VPS34 complex—at the crossroads of autophagy and beyond. Trends Cell Biol. 20, 355 (2010).
3
Berry D. L., Baehrecke E. H., Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 131, 1137 (2007).
4
Mathew R., et al., Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062 (2009).
5
Kanki T., Wang K., Cao Y., Baba M., Klionsky D. J., Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev. Cell 17, 98 (2009).
6
Okamoto K., Kondo-Okamoto N., Ohsumi Y., Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev. Cell 17, 87 (2009).
7
Geisler S., et al., PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 12, 119 (2010).
8
Narendra D., Tanaka A., Suen D. F., Youle R. J., Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183, 795 (2008).
9
Efeyan A., Sabatini D. M., mTOR and cancer: Many loops in one pathway. Curr. Opin. Cell Biol. 22, 169 (2010).
10
Shackelford D. B., Shaw R. J., The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563 (2009).
11
Zhao J., et al., FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6, 472 (2007).
12
Zhang H., et al., Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 283, 10892 (2008).
13
Eng C. H., Yu K., Lucas J., White E., Abraham R. T., Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci. Signal. 3, ra31 (2010).
14
Takeshige K., Baba M., Tsuboi S., Noda T., Ohsumi Y., Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J. Cell Biol. 119, 301 (1992).
15
Onodera J., Ohsumi Y., Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation. J. Biol. Chem. 280, 31582 (2005).
16
Lum J. J., et al., Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120, 237 (2005).
17
Tsukamoto S., et al., Autophagy is essential for preimplantation development of mouse embryos. Science 321, 117 (2008).
18
Kuma A., et al., The role of autophagy during the early neonatal starvation period. Nature 432, 1032 (2004).
19
Mizushima N., Yamamoto A., Matsui M., Yoshimori T., Ohsumi Y., In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101 (2004).
20
Kanamori H., et al., Functional significance and morphological characterization of starvation-induced autophagy in the adult heart. Am. J. Pathol. 174, 1705 (2009).
21
Komatsu M., et al., Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425 (2005).
22
Oku M., Sakai Y., Peroxisomes as dynamic organelles: autophagic degradation. FEBS J. 277, 3289 (2010).
23
Singh R., et al., Autophagy regulates lipid metabolism. Nature 458, 1131 (2009).
24
Singh R., et al., Autophagy regulates adipose mass and differentiation in mice. J. Clin. Invest. 119, 3329 (2009).
25
Zhang Y., et al., Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc. Natl. Acad. Sci. U.S.A. 106, 19860 (2009).
26
Ebato C., et al., Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab. 8, 325 (2008).
27
Jung H. S., et al., Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab. 8, 318 (2008).
28
Yang L., Li P., Fu S., Calay E. S., Hotamisligil G. S., Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab. 11, 467 (2010).
29
Rodriguez A., et al., Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab. 3, 211 (2006).
30
Cuervo A. M., Dice J. F., Age-related decline in chaperone-mediated autophagy. J. Biol. Chem. 275, 31505 (2000).
31
Hara T., et al., Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885 (2006).
32
Komatsu M., et al., Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880 (2006).
33
Komatsu M., et al., Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149 (2007).
34
Cadwell K., et al., A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259 (2008).
35
Kapahi P., et al., With TOR, less is more: A key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 11, 453 (2010).
36
Degenhardt K., et al., Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51 (2006).
37
White E., DiPaola R. S., The double-edged sword of autophagy modulation in cancer. Clin. Cancer Res. 15, 5308 (2009).
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Published In
Science
Volume 330 | Issue 6009
3 December 2010
3 December 2010
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Copyright © 2010, American Association for the Advancement of Science.
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Published in print: 3 December 2010
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- Joshua D. Rabinowitz,
- Eileen White
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