Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 311

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

Regulation of Liver Metabolism by Autophagy

Open access
Madrigal-Matute, Julio, Cuervo, Ana Maria·2016·Gastroenterology
DOI 10.1053/j.gastro.2015.09.042
Open this paper in CoChat — free account

Abstract

Intracellular components must be recycled for cells to maintain energy and ensure quality control of proteins and organelles. Autophagy is a highly conserved recycling process that involves degradation of cellular constituents in lysosomes. Although autophagy regulates a number of cell functions, it was first found to maintain energy balance in liver cells. As our understanding of autophagy has increased, we have found its connections to energy regulation in liver cells to be tight and complex. We review three mechanisms by which hepatic autophagy monitors and regulates cellular metabolism. Autophagy provides essential components (amino acids, lipids and carbohydrates) required to meet the cell’s energy needs, and it also regulates energy supply by controlling the number, quality, and dynamics of the mitochondria. Lastly, autophagy also modulates levels of enzymes in metabolic pathways. In light of the multiple ways in which autophagy participates to control liver metabolism, it is no surprise that dysregulation of autophagy has been associated with metabolic diseases such as obesity, diabetes, or metabolic syndrome, as well as liver-specific disorders such as fatty liver, non-alcoholic steatohepatitis and hepatocellular carcinoma. We discuss some of these connections and how hepatic autophagy might serve as a therapeutic target in common metabolic disorders.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1053/j.gastro.2015.09.042

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 25 references

Research works printed but not linked: 64

  1. Singh, 2011, Autophagy in the cellular energetic balance, Cell Metab, 13, 495, 10.1016/j.cmet.2011.04.004 · DOI · Paper page
  2. Mizushima, 2005, The pleiotropic role of autophagy: from protein metabolism to bactericide, Cell Death Differ, 12, 1535, 10.1038/sj.cdd.4401728 · DOI · Paper page
  3. Ezaki, 2011, Liver autophagy contributes to the maintenance of blood glucose and amino acid levels, Autophagy, 7, 727, 10.4161/auto.7.7.15371 · DOI · Paper page
  4. Cecconi, 2008, The role of autophagy in mammalian development: cell makeover rather than cell death, Dev Cell, 15, 344, 10.1016/j.devcel.2008.08.012 · DOI · Paper page
  5. Lemasters, 2014, Variants of mitochondrial autophagy: types 1 and 2 mitophagy and micromitophagy (type 3), Redox Biol, 2, 749, 10.1016/j.redox.2014.06.004 · DOI · Paper page
  6. Zhu, 2013, After the banquet: mitochondrial biogenesis, mitophagy, and cell survival, Autophagy, 9, 1663, 10.4161/auto.24135 · DOI · Paper page
  7. Schneider, 2014, Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation, Cell Metab, 20, 417, 10.1016/j.cmet.2014.06.009 · DOI · Paper page
  8. Shpilka, 2015, Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast, Proc Natl Acad Sci U S A, 112, 1434, 10.1073/pnas.1409476112 · DOI
  9. Shen, 2014, At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy, Trends Biochem Sci, 39, 61, 10.1016/j.tibs.2013.12.001 · DOI · Paper page
  10. Kaushik, 2012, Chaperone-mediated autophagy: a unique way to enter the lysosome world, Trends Cell Biol, 22, 407, 10.1016/j.tcb.2012.05.006 · DOI · Paper page
  11. Bejarano, 2014, Connexins modulate autophagosome biogenesis, Nat Cell Biol, 16, 401, 10.1038/ncb2934 · DOI
  12. Settembre, 2013, TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop, Nat Cell Biol, 15, 647, 10.1038/ncb2718 · DOI · Paper page
  13. O'Rourke, 2013, MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability, Nat Cell Biol, 15, 668, 10.1038/ncb2741 · DOI · Paper page
  14. Martina, 2014, The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris, Sci Signal, 7, ra9, 10.1126/scisignal.2004754 · DOI · Paper page
  15. Seok, 2014, Transcriptional regulation of autophagy by an FXR-CREB axis, Nature, 516, 108, 10.1038/nature13949 · DOI · Paper page
  16. Lee, 2014, Nutrient-sensing nuclear receptors coordinate autophagy, Nature, 516, 112, 10.1038/nature13961 · DOI
  17. Dice, 1990, Peptide sequences that target cytosolic proteins for lysosomal proteolysis, Trends Biochem Sci, 15, 305, 10.1016/0968-0004(90)90019-8 · DOI · Paper page
  18. Bandyopadhyay, 2008, The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane, Mol Cell Biol, 28, 5747, 10.1128/MCB.02070-07 · DOI · Paper page
  19. Cuervo, 2000, Regulation of lamp2a levels in the lysosomal membrane, Traffic, 1, 570, 10.1034/j.1600-0854.2000.010707.x · DOI · Paper page
  20. Cuervo, 1995, Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation, Am J Physiol, 269, C1200, 10.1152/ajpcell.1995.269.5.C1200 · DOI · Paper page
  21. Schneider, 2014, Liver autophagy: much more than just taking out the trash, Nat Rev Gastroenterol Hepatol, 11, 187, 10.1038/nrgastro.2013.211 · DOI
  22. Anguiano, 2013, Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives, Nat Chem Biol, 9, 374, 10.1038/nchembio.1230 · DOI · Paper page
  23. Finn, 2005, Ketone bodies stimulate chaperone-mediated autophagy, J Biol Chem, 280, 25864, 10.1074/jbc.M502456200 · DOI
  24. Rodriguez-Navarro, 2012, Inhibitory effect of dietary lipids on chaperone-mediated autophagy, Proc Natl Acad Sci U S A, 109, E705, 10.1073/pnas.1113036109 · DOI · Paper page
  25. Zhang, 2008, Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function, Nat Med, 14, 959, 10.1038/nm.1851 · DOI · Paper page
  26. Mortimore, 1983, Quantitative correlation between proteolysis and macro- and microautophagy in mouse hepatocytes during starvation and refeeding, Proc Natl Acad Sci U S A, 80, 2179, 10.1073/pnas.80.8.2179 · DOI
  27. Suzuki, 2013, Selective autophagy in budding yeast, Cell Death Differ, 20, 43, 10.1038/cdd.2012.73 · DOI
  28. Uttenweiler, 2008, Microautophagy in the yeast Saccharomyces cerevisiae, Methods Mol Biol, 445, 245, 10.1007/978-1-59745-157-4_16 · DOI
  29. van Zutphen, 2014, Lipid droplet autophagy in the yeast Saccharomyces cerevisiae, Mol Biol Cell, 25, 290, 10.1091/mbc.e13-08-0448 · DOI · Paper page
  30. Han, 2012, Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway, Cell, 149, 410, 10.1016/j.cell.2012.02.044 · DOI · Paper page
  31. Settembre, 2012, A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB, EMBO J, 31, 1095, 10.1038/emboj.2012.32 · DOI · Paper page
  32. Nicklin, 2009, Bidirectional transport of amino acids regulates mTOR and autophagy, Cell, 136, 521, 10.1016/j.cell.2008.11.044 · DOI · Paper page
  33. Hers, 1963, alpha-Glucosidase deficiency in generalized glycogenstorage disease (Pompe's disease), Biochem J, 86, 11, 10.1042/bj0860011 · DOI · Paper page
  34. Jiang, 2010, Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism, J Biol Chem, 285, 34960, 10.1074/jbc.M110.150839 · DOI
  35. Kondomerkos, 2005, Glycogen autophagy in the liver and heart of newborn rats. The effects of glucagon, adrenalin or rapamycin, Histol Histopathol, 20, 689
  36. Zhang, 2015, Reduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: reversal by growth hormone, Proc Natl Acad Sci U S A, 112, 1226, 10.1073/pnas.1423643112 · DOI
  37. Schroeder, 2015, The small GTPase Rab7 as a central regulator of hepatocellular lipophagy, Hepatology, 61, 1896, 10.1002/hep.27667 · DOI · Paper page
  38. Kaushik, 2015, Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis, Nat Cell Biol, 17, 759, 10.1038/ncb3166 · DOI · Paper page
  39. Koo, 2005, The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism, Nature, 437, 1109, 10.1038/nature03967 · DOI · Paper page
  40. Manley, 2014, Suppression of autophagic flux by bile acids in hepatocytes, Toxicol Sci, 137, 478, 10.1093/toxsci/kft246 · DOI
  41. Koga, 2010, Altered lipid content inhibits autophagic vesicular fusion, FASEB J, 24, 3052, 10.1096/fj.09-144519 · DOI · Paper page
  42. Wu, 2015, Hypoxia activation of mitophagy and its role in disease pathogenesis, Antioxid Redox Signal, 22, 1032, 10.1089/ars.2014.6204 · DOI
  43. Egan, 2011, Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy, Science, 331, 456, 10.1126/science.1196371 · DOI · Paper page
  44. Ma, 2015, Regulation of TFEB-PGC1alpha axis by BECLIN-1 controls mitochondrial quality and cardiomyocyte death under stress, Mol Cell Biol, 35, 956, 10.1128/MCB.01091-14 · DOI
  45. Lv, 2011, Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth, Mol Cell, 42, 719, 10.1016/j.molcel.2011.04.025 · DOI · Paper page
  46. Kon, 2011, Chaperone-mediated autophagy is required for tumor growth, Sci Transl Med, 3, 109ra117, 10.1126/scitranslmed.3003182 · DOI · Paper page
  47. Park, 2015, Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage, Nat Commun, 6, 6823, 10.1038/ncomms7823 · DOI
  48. Jiang, 2015, Autophagy in cellular metabolism and cancer, J Clin Invest, 125, 47, 10.1172/JCI73942 · DOI
  49. Kiffin, 2004, Activation of chaperone-mediated autophagy during oxidative stress, Mol Biol Cell, 15, 4829, 10.1091/mbc.e04-06-0477 · DOI · Paper page
  50. Schneider, 2015, Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging, Aging Cell, 14, 249, 10.1111/acel.12310 · DOI
  51. Liu, 2009, Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin, J Biol Chem, 284, 31484, 10.1074/jbc.M109.033936 · DOI · Paper page
  52. Gonzalez-Rodriguez, 2014, Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD, Cell Death Dis, 5, e1179, 10.1038/cddis.2014.162 · DOI · Paper page
  53. Inami, 2011, Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression, Biochem Biophys Res Commun, 412, 618, 10.1016/j.bbrc.2011.08.012 · DOI
  54. Galluzzi, 2015, Autophagy in malignant transformation and cancer progression, EMBO J, 34, 856, 10.15252/embj.201490784 · DOI · Paper page
  55. Ding, 2008, Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma, Cancer Res, 68, 9167, 10.1158/0008-5472.CAN-08-1573 · DOI · Paper page
  56. Inami, 2011, Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells, J Cell Biol, 193, 275, 10.1083/jcb.201102031 · DOI · Paper page
  57. Shibata, 2008, Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy, Proc Natl Acad Sci U S A, 105, 13568, 10.1073/pnas.0806268105 · DOI · Paper page
  58. Yang, 2011, Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling, J Korean Med Sci, 26, 1428, 10.3346/jkms.2011.26.11.1428 · DOI
  59. Li, 2014, Resveratrol modulates autophagy and NF-kappaB activity in a murine model for treating non-alcoholic fatty liver disease, Food Chem Toxicol, 63, 166, 10.1016/j.fct.2013.08.036 · DOI
  60. Hernandez-Gea, 2012, Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues, Gastroenterology, 142, 938, 10.1053/j.gastro.2011.12.044 · DOI · Paper page
  61. Park, 2014, Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers, Nat Commun, 5, 4834, 10.1038/ncomms5834 · DOI
  62. Lin, 2013, Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice, J Hepatol, 58, 993, 10.1016/j.jhep.2013.01.011 · DOI · Paper page
  63. Marino, 2014, Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers, Autophagy, 10, 1879, 10.4161/auto.36413 · DOI
  64. Colman, 2009, Caloric restriction delays disease onset and mortality in rhesus monkeys, Science, 325, 201, 10.1126/science.1173635 · DOI · Paper page

Cited by

See all 311

Metadata

Authors
Madrigal-Matute, J., & Cuervo, A. M.
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2016-02
Volume
150
Issue
2
Pages
328-339
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2015.09.042
OpenAlex
W1845621716
Cited by
311
References
25
FWCI
18.58
Type
journal article
Language
en
Open access
green
Licence
  • www.elsevier.com/tdm/userlicense/1.0/ (tdm)
  • www.elsevier.com/legal/tdmrep-license (tdm)
Funders
  • American Diabetes Association (1-15-MI-03)
  • National Institutes of Health (AG021904, AG031782, DK098408)

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

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Regulation of Liver Metabolism by Autophagy. https://app.cochat.ai/papers/10.1053/j.gastro.2015.09.042
The paper
Madrigal-Matute, J., & Cuervo, A. M. (2016). Regulation of Liver Metabolism by Autophagy. Gastroenterology. https://doi.org/10.1053/j.gastro.2015.09.042

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.