Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism.
Abstract
Autophagy is a major intracellular degradation system in which the cytoplasmic contents are degraded in the lysosome. Its fundamental and evolutionarily conserved role is adaptation to starvation. Recent studies using autophagy-defective mutants of various organisms including mammals have indeed demonstrated the importance of autophagy during starvation; however, the exact mechanism underlying this beneficial effect remains unclear. In addition, it is now apparent that autophagy is also important for cellular homeostasis even under non-starvation conditions, and both non-selective and selective types of autophagy appear to be critical for this function. Here, we discuss the role of this catabolic pathway in recycling intracellular components, with particular reference to nutrient metabolism.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The autophagy process is promoted when cells are cultured under starved conditions without amino acids.
“the autophagy process is promoted when cells are cultured under starved conditions without amino acids in the culture medium (Kuma and Mizushima, 2010).”
From Proteasome dysfunction induces muscle growth defects and protein aggregation (2014) · cites this paper as Kuma and Mizushima, 2010
Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026 · see citing works
Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Self-citationThe roles of intracellular protein-degradation pathways in neurodegeneration
Rubinsztein, D. C. (2006) · Nature · doi:10.1038/nature05291 · Cited by 1,625 · see citing works
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
Autophagy is required to maintain muscle mass.
Masiero, E., Agatea, L., Mammucari, C., Blaauw, B., Loro, E., Komatsu, M., Metzger, D., Reggiani, C., Schiaffino, S., & Sandri, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.008 · Cited by 1,282 · see citing works
The role of the Atg1/ULK1 complex in autophagy regulation
Mizushima, N. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.004 · Cited by 1,062 · see citing works
Self-citationStructural Basis for Sorting Mechanism of p62 in Selective Autophagy
Ichimura, Y., Kumanomidou, T., Sou, Y.-S., Mizushima, T., Ezaki, J., Ueno, T., Kominami, E., Yamane, T., Tanaka, K., & Komatsu, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802182200 · Cited by 803 · see citing works
Komatsu, M., Wang, Q. J., Holstein, G. R., Friedrich, V. L., Iwata, J.-I., Kominami, E., Chait, B. T., Tanaka, K., & Yue, Z. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701311104 · Cited by 614 · see citing works
Raben, N., Hill, V., Shea, L., Takikita, S., Baum, R., Mizushima, N., Ralston, E., & Plotz, P. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn292 · Cited by 352 · see citing works
Self-citationMature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62
Rodriguez, A., Durán, A., Selloum, M., Champy, M.-F., Diez-Guerra, F. J., Flores, J. M., Serrano, M., Auwerx, J., Diaz-Meco, M. T., & Moscat, J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.011 · Cited by 290 · see citing works
Nishiyama, J., Miura, E., Mizushima, N., Watanabe, M., & Yuzaki, M. (2007) · Autophagy · doi:10.4161/auto.4964 · Cited by 159 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Rabinowitz, J. D., & White, E. (2010) · Science · doi:10.1126/science.1193497 · Cited by 1,982 · see citing works
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,653 · see citing works
The autophagosome: origins unknown, biogenesis complex
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3696 · Cited by 1,307 · see citing works
The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression
B’chir, W., Maurin, A.-C., Carraro, V., Averous, J., Jousse, C., Muranishi, Y., Parry, L., Stepien, G., Fafournoux, P., & Bruhat, A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt563 · Cited by 1,162 · see citing works
“DISCUSSION Autophagy constitutes a major protective mechanism that allows stressed cells to survive by recycling macromolecules and restoring metabolic functions (49,58).”
BackgroundExercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
He, C., Bassik, M. C., Moresi, V., Sun, K., Wei, Y., Zou, Z., An, Z., Loh, J., Fisher, J., Sun, Q., et al. (2012) · Nature · doi:10.1038/nature10758 · Cited by 1,136 · see citing works
“For long-term exercise training, male Bcl2WT or Bcl2AAA mice (8 weeks old) were randomly divided into three cohorts, including: (1) mice fed a regular diet (Harlan Teklad) without daily exercise, (2) mice fed a HFD containing 60% fat (Research Diets) without daily exercise, and (3) mice fed a HFD with daily exercise.”
MethodHistorical landmarks of autophagy research
Ohsumi, Y. (2013) · Cell Research · doi:10.1038/cr.2013.169 · Cited by 1,093 · see citing works
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment
Amaravadi, R. K., Lippincott‐Schwartz, J., Yin, X., Weiss, W. A., Takebe, N., Timmer, W. C., DiPaola, R. S., Lotze, M. T., & White, E. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2634 · Cited by 899 · see citing works
“They include distinct steps for AV production and turnover, including (1) initiation, (2) nucleation of, and (3) maturation of AVs, and (4) fusion and degradation of AV contents in lysosomes (Fig.”
BackgroundAutophagy as a target for anticancer therapy
Jankú, F., McConkey, D. J., Hong, D. S., & Kurzrock, R. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.71 · Cited by 803 · see citing works
“Proteins degraded through autophagy are recognized by autophagy receptors, such as p62 or Nbr1, which interact with the ubiquitin-like protein LC3 that modifies target proteins for delivery to autophagosomes”
BackgroundLysosomal storage disorders: The cellular impact of lysosomal dysfunction
Platt, F. M., Boland, B., & van der Spoel, A. C. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201208152 · Cited by 689 · see citing works
“…type II (I-cell disease) N-acetyl glucosamine phosphoryl transferase / (GNPTAB) Carbohydrates, lipids, proteins Skeleton, heart + Mucolipidosis type IIIA (pseudo-Hurler polydystrophy) N-acetyl glucosamine phosphoryl transferase / (GNPTAB) Carbohydrates, lipids, proteins Skeleton, heart +/”
Autophagy: for better or for worse
Wirawan, E., Berghe, T. V., Lippens, S., Agostinis, P., & Vandenabeele, P. (2011) · Cell Research · doi:10.1038/cr.2011.152 · Cited by 468 · see citing works
Amino acid homeostasis and signalling in mammalian cells and organisms
Bröer, S., & Bröer, A. (2017) · Biochemical Journal · doi:10.1042/bcj20160822 · Cited by 496 · see citing works
Gómez-Virgilio, L., Silva-Lucero, M.-D.-C., Flores-Morelos, D.-S., Gallardo-Nieto, J., Lopez-Toledo, G., Abarca-Fernandez, A.-M., Zacapala-Gómez, A.-E., Luna-Muñoz, J., Montiel-Sosa, F., Soto-Rojas, L. O., et al. (2022) · Cells · doi:10.3390/cells11152262 · Cited by 431 · see citing works
Sahani, M. H., Itakura, E., & Mizushima, N. (2014) · Autophagy · doi:10.4161/auto.27344 · Cited by 363 · see citing works
“It is generally believed that autophagy-derived amino acids during starvation are used for protein synthesis, energy production, and gluconeogenesis.(4,37) In yeast, amino acids produced by starvation-induced autophagy are important for synthesis of amino acid biosynthetic enzymes (e.”
Self-citationOu, X., Lee, M. R., Huang, X., Messina‐Graham, S., & Broxmeyer, H. E. (2014) · Stem Cells · doi:10.1002/stem.1641 · Cited by 336 · see citing works
“Autophagy deficient mice, such as Atg3, Atg5 or Atg7 knockout mice, die at birth, indicating that autophagy inhibits cell death [36].”
BackgroundLazova, R., Camp, R. L., Klump, V., Siddiqui, S. F., Amaravadi, R. K., & Pawelek, J. M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1282 · Cited by 305 · see citing works
“org Clin Cancer Res; 18(2) January 15, 2012 375”
BackgroundInfluentialLipid Droplets in Health and Disease
Önal, G., Kutlu, O., Gozuacik, D., & Emre, S. D. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0521-7 · Cited by 279 · see citing works
“Cellular building blocks are then released back to cytosol and recycled to ensure cellular homeostasis [11, 12].”
Transcriptional Regulation of Autophagy: Mechanisms and Diseases
Di Malta, C., Cinque, L., & Settembre, C. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00114 · Cited by 255 · see citing works
Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential
Yang, D., Livingston, M. J., Liu, Z., Dong, G., Zhang, M., Chen, J.-K., & Dong, Z. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2639-1 · Cited by 252 · see citing works
“Autophagy is involved in physiology such as cell differentiation, animal development and nutrient metabolism [32, 33].”
BackgroundMolecules and their functions in autophagy
Pyo, J.-O., Nah, J., & Jung, Y. (2012) · Experimental & Molecular Medicine · doi:10.3858/emm.2012.44.2.029 · Cited by 252 · see citing works
“Unlike in yeast, however, the ULK1 kinase complex in mammal is likely to be stably formed for autophagosome formation regardless of nutrient conditions (Ganley et al., 2009; Mercer et al., 2009; Kuma and Mizushima, 2010).”
BackgroundAutophagy and oxidative stress in cardiovascular diseases
Mei, Y., Thompson, M. D., Cohen, R. A., & Tong, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.005 · Cited by 243 · see citing works
“The Atg1/ULK1 complex (Atg1 in yeast and ULK1 in mammals) is an initial regulator of autophagosome formation [34].”
BackgroundFerraro, E., Giammarioli, A. M., Chiandotto, S., Spoletini, I., & Rosano, G. M. C. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5773 · Cited by 265 · see citing works
“It primarily favors survival during nutritional stress imposed by decreased nutrients; the degradation of intracellular material through autophagy becomes an alternative source of energy (83, 91).”
BackgroundAMP-activated protein kinase, stress responses and cardiovascular diseases
Wang, S., Song, P., & Zou, M. (2012) · Clinical Science · doi:10.1042/cs20110625 · Cited by 243 · see citing works
Chloroquine and hydroxychloroquine for cancer therapy
Manic, G., Obrist, F., Kroemer, G., Vitale, I., & Galluzzi, L. (2014) · Molecular & Cellular Oncology · doi:10.4161/mco.29911 · Cited by 223 · see citing works
“The products of the degradation of the autophagic cargo eventually reach the cytosol through lysosomal permeases, hence becoming available for reuse in biosynthetic metabolic circuitries.(12) A detailed description of the autophagic machinery and its regulators goes largely beyond the scope of the present Trial Watch…”
BackgroundDopamine Oxidation and Autophagy
Muñoz, P., Huenchuguala, S., Paris, I., & Segura-Aguilar, J. (2012) · Parkinson's Disease · doi:10.1155/2012/920953 · Cited by 214 · see citing works
“Autophagy is an important intracellular bulk degradation and recycling process in which cytoplasmic proteins and organelles accumulate in autophagy vacuoles that are transported into lysosomes [58–60].”
BackgroundRole of autophagy in cancer prevention
Chen, H.-Y., & White, E. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0387 · Cited by 190 · see citing works
“cated nutrient stores for energy production and biomass production under stress (4, 60).”
BackgroundSuzuki, S. W., Onodera, J., & Ohsumi, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017412 · Cited by 169 · see citing works
“Accumulating data indicate that autophagy plays important roles in maintaining cellular homeostasis, and is relevant to several diseases [6,7].”
Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer's Disease
Kan, M. J., Lee, J. E., Wilson, J. G., Everhart, A. L., Brown, C. M., Hoofnagle, A. N., Jansen, M., Vitek, M. P., Gunn, M. D., & Colton, C. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4668-14.2015 · Cited by 174 · see citing works
“Sustained arginine deprivation leads to cell death (Kuma and Mizushima, 2010).”
BackgroundAutophagy Is Rapidly Induced by Salt Stress and Is Required for Salt Tolerance in Arabidopsis
Luo, L.-M., Zhang, P., Zhu, R., Fu, J., Su, J., Zheng, J., Wang, Z., Wang, D., & Gong, Q.-Q. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01459 · Cited by 158 · see citing works
“The inner membrane of the autophagosome along with the cargo, termed the autophagic body, is then degraded by vacuolar hydrolases, and amino acids and other macro molecules are released back into the cytosol through transporters (Kuma and Mizushima, 2010; Shibutani and Yoshimori, 2014).”
The variability of autophagy and cell death susceptibility
Loos, B., Engelbrecht, A., Lockshin, R. A., Klionsky, D. J., & Zakeri, Z. (2013) · Autophagy · doi:10.4161/auto.25560 · Cited by 148 · see citing works
Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice
Moresi, V., Carrer, M., Grueter, C. E., Rifki, O. F., Shelton, J. M., Richardson, J. A., Bassel‐Duby, R., & Olson, E. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121159109 · Cited by 143 · see citing works
“The process involves formation of vesicles, called autophagosomes, that capture and deliver proteins to lysosomes for degradation (1).”
BackgroundHeaton, N. S., & Randall, G. (2011) · Viruses · doi:10.3390/v3081332 · Cited by 136 · see citing works
“LC3-II plays critical roles in cargo identification and membrane fusion [8].”
BackgroundThe PI3K, Metabolic, and Autophagy Networks: Interactive Partners in Cellular Health and Disease
Shanware, N. P., Bray, K., & Abraham, R. T. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134717 · Cited by 130 · see citing works
Autophagy, Stress, and Cancer Metabolism: What Doesn't Kill You Makes You StrongerPreprint
Mathew, R., & White, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.011015 · Cited by 123 · see citing works
“A simultaneous increase in the AMP/ATP ratio leads to the activation of AMPK by the LKB1/STRAD/MO25 complex (Kuma and Mizushima 2010; Neufeld 2010), which activates autophagy by ULK1 phosphorylation (Egan et al. 2011), as well as through inhibition of mTORC1 (Gwinn et al. 2008).”
BackgroundSchläfli, A. M., Adams, O., Galván, J., Gugger, M., Savic, S., Bubendorf, L., Schmid, R., Becker, K., Tschan, M., Langer, R., et al. (2016) · OncoTarget · doi:10.18632/oncotarget.9647 · Cited by 129 · see citing works
“The cellular process of autophagy has many functions including bulk degradation of cytoplasmic content to ensure homeostasis [2], degradation of superfluous or damaged organelles [3] and the engulfment Research Paper”
BackgroundCai, Z.-Y., Zhao, B., Li, K.-S., Zhang, L.-Q., Li, C., Quazi, S. H., & Tan, Y. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23011 · Cited by 129 · see citing works
“Autophagy, a response to nutrient starvation and stress, is a housekeeping process whereby long-lived proteins and organelles, such as mitochondria, are recycled (Wu et al., 2009; Kuma and Mizushima, 2010).”
BackgroundZhao, H., Yang, M., Zhao, J., Wang, J., Zhang, Y., & Zhang, Q. (2013) · Medical Oncology · doi:10.1007/s12032-013-0475-1 · Cited by 124 · see citing works
“On the other hand, some researches have shown that the cellular components which are degraded by autophagolysosomes can provide amino acids, nucleotides, and lipids for ATP production and molecular synthesis of cancer cell [6].”
BackgroundGenome‐wide siRNA screen reveals amino acid starvation‐induced autophagy requires SCOC and WAC
McKnight, N. C., Jefferies, H. B., Alemu, E. A., Saunders, R., Howell, M., Johansen, T., & Tooze, S. A. (2012) · EMBO Journal · doi:10.1038/emboj.2012.36 · Cited by 118 · see citing works
“Autophagy is also induced in response to amino-acid deprivation or external stress, recycling macromolecules and restoring metabolic functions (Kuma and Mizushima, 2010).”
Balancing nutrient and energy demand and supply via autophagy
He, C. (2022) · Current Biology · doi:10.1016/j.cub.2022.04.071 · Cited by 137 · see citing works
Seldin, M. M., Lei, X., Tan, S. Y., Stanson, K. P., Wei, Z., & Wong, G. W. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.500736 · Cited by 120 · see citing works
“Prolonged periods of food deprivation turn on autophagy, the cell recycling pathway, by inducing the expression of autophagy-related genes and the formation of autophagosomes (1).”
BackgroundInfluentialAutophagy modulates cell migration and β1 integrin membrane recycling
Tuloup-Minguez, V., Hamaï, A., Greffard, A., Nicolas, V., Codogno, P., & Botti, J. (2013) · Cell Cycle · doi:10.4161/cc.26298 · Cited by 99 · see citing works
“Activation of this kinase in the MTOR complex 1 (MTORC1) is known to be a major repressor of autophagy.(10,16,18) Treatment with rapamycin, a MTORC1 inhibitor, stimulates autophagy and reduces cell migration.”
BackgroundHuang, G., Zhang, F.-M., Ye, Q., & Wang, H. (2016) · Autophagy · doi:10.1080/15548627.2016.1183843 · Cited by 104 · see citing works
“mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) phosphorylates the ULK1 protein and inhibits autophagy initiation when nutrients are abundant.(12) Genetic disruption of autophagy genes promotes tumorigenesis and accumulation of ubiquitinated protein aggregates.”
BackgroundRole of autophagy in disease resistance and hypersensitive response-associated cell death
Hofius, D., Munch, D., Bressendorff, S., Mundy, J., & Petersen, M. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.43 · Cited by 101 · see citing works
Rubicon: <scp>LC</scp>3‐associated phagocytosis and beyond
Wong, S., Sil, P., & Martinez, J. (2018) · The FEBS Journal · doi:10.1111/febs.14354 · Cited by 101 · see citing works
Garay, E., Campos, S. E., de la Cruz, J. G., Gaspar, A. P., Jinich, A., & DeLuna, A. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004168 · Cited by 96 · see citing works
Pompe disease: pathogenesis, molecular genetics and diagnosis
Taverna, S., Cammarata, G., Colomba, P., Sciarrino, S., Zizzo, C., Francofonte, D., Zora, M., Scalia, S., Brando, C., Curto, A. L., et al. (2020) · Aging · doi:10.18632/aging.103794 · Cited by 121 · see citing works
Maycotte, P., & Thorburn, A. M. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14627 · Cited by 394 · see citing works
“In fact, amino acid levels in autophagy deficient mice (atg 3, 5, 7, 9 and atg16L1 knockout mice) are lower than in wild type mice after birth and although these mice appear normal, they die within 1 day since they cannot survive the neonatal starvation period due to termination of the transplacental nutrient supply.(…”
Backgroundvan der Sloot, K. W. J., Amini, M., Peters, V., Dijkstra, G. D. H., & Alizadeh, B. Z. (2017) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000001217 · Cited by 92 · see citing works
Role of autophagy in aging: The good, the bad, and the ugly
TABIBZADEH, S. S. (2022) · Aging Cell · doi:10.1111/acel.13753 · Cited by 103 · see citing works
“There is a conundrum in the relationship of autophagy and senescence, since autophagy appears to have both anti and prosenescence effects (Kwon et al., 2017).”
BackgroundBai, J.-R., Liu, T., Tu, B., Yuan, M., Shu, Z., Fan, M., Huo, S.-H., Guo, Y., Wang, L.-N., Wang, H., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2093026 · Cited by 91 · see citing works
“As we know, autophagy is an important process of replenishing amino acids when cells faced nutrientdeprived environments [17].”
BackgroundBharath, L. P., Cho, J. M., Park, S.-K., Ruan, T., Li, Y., Mueller, R., Bean, T., Reese, V. R., Richardson, R. S., Cai, J., et al. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309510 · Cited by 96 · see citing works
Danon disease – dysregulation of autophagy in a multisystem disorder with cardiomyopathy
Rowland, T., Sweet, M., Mestroni, L., & Taylor, M. (2016) · Journal of Cell Science · doi:10.1242/jcs.184770 · Cited by 88 · see citing works
“…mitochondria, ribosomes, peroxisomes, endoplasmic reticulum and additional membrane structures, glycogen, lipid granules and other cytosolic aggregates (Kovsan et al., 2010; Kundu et al., 2008; Kuma and Mizushima, 2010; Schneider and Cuervo, 2014; Shires and Gustafsson, 2015; Nishida et al., 2015).”
BackgroundmTOR Activity and Autophagy in Senescent Cells, a Complex Partnership
Cayo, Á., Segovia, R., Venturini, W., Moore‐Carrasco, R., Valenzuela, C. A., & Brown, N. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158149 · Cited by 92 · see citing works
The influence of circular RNAs on autophagy and disease progression
Wang, Y., Mo, Y., Miao, P., Zhang, S., Gong, Z., Yan, Q., Tang, Y., He, Y., Liao, Q., Li, X., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1917131 · Cited by 99 · see citing works
“However, when stimulated by metabolic changes [10,11], oxidative stress [12], endoplasmic reticulum stress [13], mechanical damage [14,15], or protein aggregation [16,17], cells respond by swallowing and digesting aged or damaged organelles, or misfolded or accumulated proteins, to maintain homeostasis.”
BackgroundYoung, C., Sinadinos, A., Lefebvre, A., Chan, P., Arkle, S., Vaudry, D., & Górecki, D. C. (2015) · Autophagy · doi:10.4161/15548627.2014.994402 · Cited by 84 · see citing works
Cellular and Molecular Mechanisms of Insect Immunity
Rosales, C. (2017) · InTech eBooks · doi:10.5772/67107 · Cited by 81 · see citing works
“In this manner, the degradative process of autophagy helps recycle nutrients and maintains cellular homeostasis [179].”
BackgroundProteasome dysfunction induces muscle growth defects and protein aggregation
Kitajima, Y., Tashiro, Y., Suzuki, N., Warita, H., Kato, M., Tateyama, M., Ando, R., Izumi, R., Yamazaki, M., Abe, M., et al. (2014) · Journal of Cell Science · doi:10.1242/jcs.150961 · Cited by 79 · see citing works
“process is promoted when cells are cultured under starved conditions without amino acids in the culture medium (Kuma and Mizushima, 2010).”
BackgroundRole of autophagy in intervertebral disc degeneration
Kritschil, R., Scott, M. J., Sowa, G., & Vo, N. N. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30631 · Cited by 84 · see citing works
“Macroautophagy herein referred to as autophagy, is a well‐ established intracellular survival mechanism vital for cell function (Kuma & Mizushima, 2010).”
BackgroundInfluentialGuo, B., Tam, A., Santi, S., & Parissenti, A. (2016) · BMC Cancer · doi:10.1186/s12885-016-2790-3 · Cited by 79 · see citing works
“autophagy occurs in all cells to ensure that only functional organelles are retained [4].”
Kuramoto, K., Liang, H., Hong, J., & He, C. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.011 · Cited by 86 · see citing works
Autophagy supports survival and phototransduction protein levels in rod photoreceptors
Zhou, Z., Doggett, T. A., Sène, A., Apte, R. S., & Ferguson, T. A. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2014.229 · Cited by 78 · see citing works
“hypoxia), autophagy is activated immediately (induced autophagy).(6) Induced autophagy maintains the amino acid pool”
BackgroundNaito, T., Kuma, A., & Mizushima, N. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.456228 · Cited by 86 · see citing works
“The induced autophagy is important for providing amino acids and other factors, which can be used for synthesis of proteins and other metabolites, energy production, and gluconeogenesis under starvation conditions (4, 6).”
BackgroundSelf-citationAutophagy Modulators: Mechanistic Aspects and Drug Delivery Systems
Tavakol, S., Ashrafizadeh, M., Deng, S., Azarian, M., Abdoli, A., Motavaf, M., Poormoghadam, D., Khanbabaei, H., Afshar, E. G., Mandegary, A., et al. (2019) · Biomolecules · doi:10.3390/biom9100530 · Cited by 89 · see citing works
Chloroquine and nanoparticle drug delivery: A promising combination
Pelt, J., Busatto, S., Mauro Ferrari, B., Thompson, E. A., Mody, K., & Wolfram, J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.007 · Cited by 82 · see citing works
Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle
Fritzen, A. M., Frøsig, C., Jeppesen, J. F., Jensen, T. E., Lundsgaard, A., Serup, A. K., Schjerling, P., Proud, C. G., Richter, E. A., & Kiens, B. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.005 · Cited by 82 · see citing works
Oral, Ö., Akkoç, Y., Bayraktar, O., & Gözüaçık, D. (2016) · PubMed · doi:10.14670/hh-11-714 · Cited by 75 · see citing works
“After the fusion of the outer membrane with lysosomes, the inner membrane and the cargo are degraded by hydrolytic enzymes in lysosomes and then its constituents are recycled (Gozuacik and Kimchi, 2007; Kuma and Mizushima, 2010).”
BackgroundAutophagy in Toxicology: Cause or Consequence?
Orrenius, S., Kaminskyy, V. O., & Zhivotovsky, B. (2012) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140210 · Cited by 81 · see citing works
TFEB Biology and Agonists at a Glance
Chen, M., Dai, Y., Liu, S., Fan, Y., Ding, Z.-X., & Li, D. (2021) · Cells · doi:10.3390/cells10020333 · Cited by 73 · see citing works
Wang, J.-Q., Wen, X., Zhang, Y.-Y., Zou, P., Cheng, L., Gan, R.-Y., Li, X., Liu, D.-Y., & Geng, F. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.127884 · Cited by 71
Role of Autophagy in Lung Inflammation
Painter, J. D., Galle-Treger, L., & Akbari, O. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01337 · Cited by 79 · see citing works
“This vesicle is called an autophagosome and when fused with the lysosome it becomes an autolysosome containing all the hydrolytic enzymes needed to break down its contents (4).”
BackgroundAmino Acid Homeostasis in Mammalian Cells with a Focus on Amino Acid Transport
Bröer, S., & Gauthier-Coles, G. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab342 · Cited by 80 · see citing works
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.
Paris, I., Muñoz, P., Huenchuguala, S., Couve, E., Sanders, L. H., Greenamyre, J., Caviedes, P., & Segura-Aguilar, J. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr060 · Cited by 69 · see citing works
“However, autophagy is also an intracellular bulk degradation process whereby cytoplasm proteins and organelles are degraded and recycled through lysosomes (Kuma and Mizushima, 2010; Matsui et al., 2008; Tettamanti et al., 2008).”
BackgroundThe filamentous fungus Sordaria macrospora as a genetic model to study fruiting body development.
Teichert, I., Nowrousian, M., Pöggeler, S., & Kück, U. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00004-4 · Cited by 64 · see citing works
“It is a lysosome/vacuole-dependent degradation process for the recycling of macromolecular building blocks and the removal of surplus, aberrant, or defective cell constituents (Kuma & Mizushima, 2010).”
BackgroundCui, M., Yu, H. K., Wang, J., Gao, J., & Li, J. (2013) · Journal of Diabetes Research · doi:10.1155/2013/852754 · Cited by 65 · see citing works
“Autophagy is an intracellular recycling pathway that functions during basal conditions but can be induced under stress such as starvation [6].”
BackgroundRegulation of Exercise-Induced Autophagy in Skeletal Muscle
Rocchi, A., & He, C. (2017) · Current Pathobiology Reports · doi:10.1007/s40139-017-0135-9 · Cited by 68 · see citing works
Sporadic Alzheimer's Disease: The Starving Brain
Mamelak, M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120370 · Cited by 56 · see citing works
“These lipoproteins considered the most atherogenic of the lipoproteins.”
How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer
Ferraresi, A., Girone, C., Esposito, A., Vidoni, C., Vallino, L., Secomandi, E., Dhanasekaran, D. N., & Isidoro, C. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.599915 · Cited by 61 · see citing works
“The sequestered cargo is degraded by lysosomal acid hydrolases into monomeric constituents that are exported across the lysosomal membrane to the cytosol for re-use during cellular renovation and macromolecules turnover (22).”
BackgroundA ravenous defense: canonical and non-canonical autophagy in immunity
Sil, P., Muse, G. W., & Martinez, J. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.10.004 · Cited by 65 · see citing works
Loos, B., Klionsky, D. J., & Wong, E. S. P. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.05.001 · Cited by 61 · see citing works
Sorafenib-induced defective autophagy promotes cell death by necroptosis
Kharaziha, P., Chioureas, D., Baltatzis, G., Fonseca, P., Rodriguez, P. Q., Gogvadze, V. G., Lennartsson, L., Björklund, A.-C., Zhivotovsky, B., Grandér, D., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5797 · Cited by 56 · see citing works
“It is a cytoprotective, physiological process that maintains homeostasis by relieving the cell from cytotoxic, damaged organelles as well as support survival during conditions of metabolic stress [15, 16].”
BackgroundThe Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury
Lv, S., Liu, H., & Wang, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168773 · Cited by 60 · see citing works
“Autophagosomes fuse with lysosomes to become autolysosomes in which hydrolases degrade the contents [5].”
BackgroundEmerging roles of autophagy in metabolism and metabolic disorders
Rocchi, A., & He, C. (2015) · Frontiers in Biology · doi:10.1007/s11515-015-1354-2 · Cited by 65 · see citing works
“Autophagy occurs constitutively at a low level, which is important for intracellular quality control through constitutive turnover of cytoplasmic component (Kuma and Mizushima, 2010).”
BackgroundAutophagy as a crosstalk mediator of metabolic organs in regulation of energy metabolism
Kim, K. H., & Lee, M. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9272-6 · Cited by 49 · see citing works
Cheng, N., Guo, A., & Meng, H. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-0995-x · Cited by 50 · see citing works
“The most important characteristic of autophagy is the formation of autophagosomes [15], they fuse with lysosomes to form autolysosomes, and then the contents in autolysosomes will be degraded by lysosomal enzyme [16].”
BackgroundMuñoz, P., Paris, I., Sanders, L. H., Greenamyre, J., & Segura-Aguilar, J. (2012) · Biochimica et Biophysica Acta · doi:10.1016/j.bbadis.2012.03.010 · Cited by 49 · see citing works
Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy
Jang, Y., Choi, K.-S., & Min, D. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.174 · Cited by 47 · see citing works
“The ATG1/ULK1 complex (Atg1 in yeast and ULK1 in mammals) is an essential positive regulator of autophagosome formation.(9) mTOR serves as a major intracellular hub for integration of autophagy-related signals.”
BackgroundTamtaji, O., Hadinezhad, T., Fallah, M., Shahmirzadi, A., Taghizadeh, M., Behnam, M., & Asemi, Z. (2019) · Current Drug Targets · doi:10.2174/1389450120666191112155654 · Cited by 45 · see citing works
Hu, H., Li, B., Wang, J., Tan, Y., Xu, M., Xu, W., & Lu, H.-J. (2023) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2023.114778 · Cited by 44 · see citing works
Hashemi, M., Nadafzadeh, N., Imani, M. H., Rajabi, R., Ziaolhagh, S., Bayanzadeh, S. D., Norouzi, R., Rafiei, R., Koohpar, Z. K., Raei, B., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01053-z · Cited by 47 · see citing works
“The basic level of autophagy is required under normal conditions, but its induction can be mediated by metabolic changes [8, 9], oxidative stress [10], endoplasmic reticulum stress [11], mechanical damage [12, 13], and misfolded protein accumulation [14, 15].”
BackgroundInhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells
Guo, W., Wang, Y., Wang, Z., Wang, Y., & Zheng, H. (2016) · Cancer Science · doi:10.1111/cas.13059 · Cited by 44 · see citing works
Autophagy mechanism and physiological relevance brewed from yeast studies
Devenish, R. J. (2012) · Frontiers in Bioscience-Scholar · doi:10.2741/s337 · Cited by 35 · see citing works
“An induction signal (1) leads to the commencement of phagophore formation (2).”
BackgroundQuercetin Regulates the Integrated Stress Response to Improve Memory
Nakagawa, T., & Ohta, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112761 · Cited by 43 · see citing works
“Since autophagy plays a role in the recycling of amino acids, glucose, and lipids, autophagy is induced when cells are exposed to amino acid starvation [61].”
BackgroundTHOMAS, M. P., Davis, T., Loos, B., Sishi, B., Huisamen, B., Strijdom, H., & Engelbrecht, A. (2018) · Cell Biochemistry and Function · doi:10.1002/cbf.3318 · Cited by 41 · see citing works
Paraoxonases and chemokine (C-C motif) ligand-2 in noncommunicable diseases.
Camps, J., Rodríguez-Gallego, E., García-Heredia, A., Triguero, I., Riera-Borrull, M., Hernández-Aguilera, A., Luciano-Mateo, F., Fernández-Arroyo, S., & Joven, J. (2014) · Advances in Clinical Chemistry · doi:10.1016/b978-0-12-800094-6.00007-8 · Cited by 41 · see citing works
Zhang, T., Guo, J., Gu, J., Chen, K., Li, H.-L., & Wang, J.-L. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/7861290 · Cited by 40 · see citing works
“In nutrient-rich conditions, autophagy holds at a low level to maintain intracellular homeostasis through the removal of long-lived and malformed proteins and damaged organelles, called basal autophagy [100].”
BackgroundAmino Acid Transporters as Disease Modifiers and Drug Targets
Bröer, S. (2018) · SLAS discovery : advancing life sciences R & D · doi:10.1177/2472555218755629 · Cited by 40 · see citing works
Role of autophagy in the maintenance and function of cancer stem cells
Vitale, I., Manic, G., Dandrea, V., & Maria, R. D. (2015) · The International Journal of Developmental Biology · doi:10.1387/ijdb.150082iv · Cited by 39 · see citing works
“…acidic hydrolases), whose catabolic activity is triggered by the activation of H+ pumps, which lowers the pH of the lysosomal lumen(Kroemer et al., 2010) Lysosomal permeases eventually promote the cytosolic export of the product of this degradation for potential reuse(Kuma and Mizushima, 2010).”
BackgroundEchavarría-Consuegra, L., Smit, J. M., & Reggiori, F. (2019) · Open Biology · doi:10.1098/rsob.190009 · Cited by 44 · see citing works
May, A. I., Prescott, M., & Ohsumi, Y. (2020) · Nature Communications · doi:10.1038/s41467-020-18805-x · Cited by 36 · see citing works
Leite, J. S. M., Cruzat, V. F., Krause, M. D. S., & de Bittencourt, P. I. H. (2016) · Nutrire · doi:10.1186/s41110-016-0021-y · Cited by 40 · see citing works
“During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism [42].”
BackgroundZhou, L., He, X., Gao, B., & Xiong, S. (2015) · Journal of Virology · doi:10.1128/jvi.01028-15 · Cited by 34 · see citing works
“The process involves the formation of vesicles, called autophagosomes, which capture and deliver protein aggregates and damaged organelles to lysosomes for degradation (41, 42).”
Background
- Authors
- Kuma, A., & Mizushima, N.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Mizushima, Noboru
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 21
- Issue
- 7
- Pages
- 683-690
- ISSN
- 1084-9521 (ISSN-L)
- OpenAlex
- W2062922078
- Cited by
- 237
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 21 · 2020: 17 · 2019: 15 · 2018: 14 · 2017: 19 · 2016: 17 · 2015: 10 · 2014: 16 · 2013: 24 · 2012: 13
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Takeda Science Foundation
- Korea Toray Science Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- autophagy, nutrient metabolism, starvation adaptation, lysosomal degradation, selective autophagy, cellular homeostasis, catabolism
- MeSH terms
- Animals, Autophagy, Cell Physiological Phenomena, Humans, Saccharomyces cerevisiae, Starvation, Metabolic Networks and Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review