Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Chaperone-Mediated Autophagy: A Potential Target for Metabolic Diseases

Author(s): Ming Yang, Shilu Luo, Wei Chen, Li Zhao and Xi Wang*

Volume 30, Issue 16, 2023

Published on: 04 October, 2022

Page: [1887 - 1899] Pages: 13

DOI: 10.2174/0929867329666220811141955

Price: $65


Autophagy is the process by which cells selectively remove damaged organelles or proteins. Chaperone-mediated autophagy (CMA) is a type of autophagy that degrades proteins containing the KFERQ pentapeptide in cells. CMA can degrade damaged or excess proteins and therefore plays an important role in maintaining protein balance in cells. CMA can also play a regulatory role by degrading key proteins in life activities, such as lipid and glucose metabolism. This review introduces the CMA process and describes the current commonly used CMA detection methods. In addition, we describe the role of CMA in glucose and lipid metabolism. Finally, we summarize the current role of CMA in metabolic diseases such as diabetic nephropathy (DN), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) and discuss the role of CMA as a potential therapeutic target for metabolic diseases.

Keywords: Chaperone-mediated autophagy (CMA), metabolic diseases, autophagy, diabetic nephropathy (DN), LAMP2A, HSC70.

« Previous
Kuma, A.; Komatsu, M.; Mizushima, N. Autophagy-monitoring and autophagy-deficient mice. Autophagy, 2017, 13(10), 1619-1628.
[] [PMID: 28820286]
Kim, K.H.; Lee, M.S. Autophagy--a key player in cellular and body metabolism. Nat. Rev. Endocrinol., 2014, 10(6), 322-337.
[] [PMID: 24663220]
Feng, Y.; He, D.; Yao, Z.; Klionsky, D.J. The machinery of macroautophagy. Cell Res., 2014, 24(1), 24-41.
[] [PMID: 24366339]
Al-Huseini, I.; Sirasanagandla, S.R.; Babu, K.S.; Sofin, R.G.S.; Das, S. Kinase inhibitors involved in the regulation of autophagy: Molecular concepts and clinical implications. Curr. Med. Chem., 2022, 29
[] [PMID: 35078392]
Li, W.W.; Li, J.; Bao, J.K. Microautophagy: Lesser-known self-eating. Cell. Mol. Life Sci., 2012, 69(7), 1125-1136.
[] [PMID: 22080117]
Jacomin, A.C.; Gohel, R.; Hussain, Z.; Varga, A.; Maruzs, T.; Eddison, M.; Sica, M.; Jain, A.; Moffat, K.G.; Johansen, T.; Jenny, A.; Juhasz, G.; Nezis, I.P. Degradation of arouser by endosomal microautophagy is essential for adaptation to starvation in Drosophila. Life Sci. Alliance, 2020, 4(2), 4.
[PMID: 33318080]
Garcia, E.J.; Liao, P.C.; Tan, G.; Vevea, J.D.; Sing, C.N.; Tsang, C.A.; McCaffery, J.M.; Boldogh, I.R.; Pon, L.A. Membrane dynamics and protein targets of lipid droplet microautophagy during ER stress-induced proteostasis in the budding yeast, Saccharomyces cerevisiae. Autophagy, 2021, 17(9), 2363-2383.
[] [PMID: 33021864]
Bourdenx, M.; Martín-Segura, A.; Scrivo, A.; Rodriguez-Navarro, J.A.; Kaushik, S.; Tasset, I.; Diaz, A.; Storm, N.J.; Xin, Q.; Juste, Y.R.; Stevenson, E.; Luengo, E.; Clement, C.C.; Choi, S.J.; Krogan, N.J.; Mosharov, E.V.; Santambrogio, L.; Grueninger, F.; Collin, L.; Swaney, D.L.; Sulzer, D.; Gavathiotis, E.; Cuervo, A.M. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell, 2021, 184(10), 2696-2714.e25.
[] [PMID: 33891876]
Nieto-Torres, J.L.; Hansen, M. Macroautophagy and aging: The impact of cellular recycling on health and longevity. Mol. Aspects Med., 2021, 82, 101020.
[] [PMID: 34507801]
Münz, C. The macroautophagy machinery in endo- and exocytosis. J. Mol. Biol., 2017, 429(4), 473-485.
[] [PMID: 27932293]
Onishi, M.; Yamano, K.; Sato, M.; Matsuda, N.; Okamoto, K. Molecular mechanisms and physiological functions of mitophagy. EMBO J., 2021, 40(3), e104705.
[] [PMID: 33438778]
Yang, M.; Luo, S.; Wang, X.; Li, C.; Yang, J.; Zhu, X.; Xiao, L.; Sun, L. ER-Phagy: A new regulator of ER homeostasis. Front. Cell Dev. Biol., 2021, 9, 684526.
[] [PMID: 34307364]
Germain, K.; Kim, P.K. Pexophagy: A model for selective autophagy. Int. J. Mol. Sci., 2020, 21(2), 21.
[] [PMID: 31963200]
Schulze, R.J.; Sathyanarayan, A.; Mashek, D.G. Breaking fat: The regulation and mechanisms of lipophagy. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2017, 1862(10 Pt B), 1178-1187.
[] [PMID: 28642194]
Schuck, S. Microautophagy - distinct molecular mechanisms handle cargoes of many sizes. J. Cell Sci., 2020, 133(17), 133.
[] [PMID: 32907930]
Mijaljica, D.; Prescott, M.; Devenish, R.J. Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum. Autophagy, 2011, 7(7), 673-682.
[] [PMID: 21646866]
Sato, M.; Seki, T.; Konno, A.; Hirai, H.; Kurauchi, Y.; Hisatsune, A.; Katsuki, H. Rapamycin activates mammalian microautophagy. J. Pharmacol. Sci., 2019, 140(2), 201-204.
[] [PMID: 31178328]
Bourdenx, M.; Gavathiotis, E.; Cuervo, A.M. Chaperone-mediated autophagy: A gatekeeper of neuronal proteostasis. Autophagy, 2021, 17(8), 2040-2042.
[] [PMID: 34110247]
Li, W.; Nie, T.; Xu, H.; Yang, J.; Yang, Q.; Mao, Z. Chaperone-mediated autophagy: Advances from bench to bedside. Neurobiol. Dis., 2019, 122, 41-48.
[] [PMID: 29800676]
Handa, K.; Kanno, H.; Matsuda, M.; Sugaya, T.; Murakami, T.; Prudnikova, M.; Ozawa, H.; Itoi, E. Chaperone-mediated autophagy after spinal cord injury. J. Neurotrauma, 2020, 37(15), 1687-1695.
[] [PMID: 32233738]
Catarino, S.; Pereira, P.; Girão, H. Molecular control of chaperone-mediated autophagy. Essays Biochem., 2017, 61(6), 663-674.
[] [PMID: 29233876]
Nie, T.; Tao, K.; Zhu, L.; Huang, L.; Hu, S.; Yang, R.; Xu, P.; Mao, Z.; Yang, Q. Chaperone-mediated autophagy controls the turnover of E3 ubiquitin ligase MARCHF5 and regulates mitochondrial dynamics. Autophagy, 2021, 17(10), 2923-2938.
[] [PMID: 33970775]
Andrade-Tomaz, M.; de Souza, I.; Rocha, C.; Gomes, L.R. The role of chaperone-mediated autophagy in cell cycle control and its implications in cancer. CELLS-BASEL, 2020, 9, 9.
Campbell, P.; Morris, H.; Schapira, A. Chaperone-mediated autophagy as a therapeutic target for Parkinson disease. Expert Opin. Ther. Targets, 2018, 22(10), 823-832.
[] [PMID: 30185079]
Yang, R.; Gao, G.; Mao, Z.; Yang, Q. Chaperone-mediated autophagy and mitochondrial homeostasis in Parkinson’s disease. Parkinsons Dis., 2016, 2016, 2613401.
[] [PMID: 27413575]
Dice, J.F. Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem. Sci., 1990, 15(8), 305-309.
[] [PMID: 2204156]
Kaushik, S.; Cuervo, A.M. The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol., 2018, 19(6), 365-381.
[] [PMID: 29626215]
Ferreira, J.V.; Soares, A.R.; Ramalho, J.S.; Pereira, P.; Girao, H. K63 linked ubiquitin chain formation is a signal for HIF1A degradation by Chaperone-mediated autophagy. Sci. Rep., 2015, 5(1), 10210.
[] [PMID: 25958982]
Bonam, S.R.; Ruff, M.; Muller, S. HSPA8/HSC70 in immune disorders: A molecular rheostat that adjusts Chaperone-mediated autophagy substrates. CELLS-BASEL, 2019, 8.
Issa, A.R.; Sun, J.; Petitgas, C.; Mesquita, A.; Dulac, A.; Robin, M.; Mollereau, B.; Jenny, A.; Chérif-Zahar, B.; Birman, S. The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy, 2018, 14(11), 1898-1910.
[] [PMID: 29989488]
Ikami, Y.; Terasawa, K.; Sakamoto, K.; Ohtake, K.; Harada, H.; Watabe, T.; Yokoyama, S.; Hara-Yokoyama, M. The two-domain architecture of LAMP2A regulates its interaction with Hsc70. Exp. Cell Res., 2022, 411(1), 112986.
[] [PMID: 34942188]
Losmanová, T.; Janser, F.A.; Humbert, M.; Tokarchuk, I.; Schläfli, A.M.; Neppl, C.; Schmid, R.A.; Tschan, M.P.; Langer, R.; Berezowska, S. Chaperone-Mediated autophagy markers LAMP2A and HSC70 are independent adverse prognostic markers in primary resected squamous cell carcinomas of the lung. Oxid. Med. Cell. Longev., 2020, 2020, 8506572.
[] [PMID: 33029283]
Kacal, M.; Zhang, B.; Hao, Y.; Norberg, E.; Vakifahmetoglu-Norberg, H. Quantitative proteomic analysis of temporal lysosomal proteome and the impact of the KFERQ-like motif and LAMP2A in lysosomal targeting. Autophagy, 2021, 17(11), 3865-3874.
[] [PMID: 33446043]
Tekirdag, K.; Cuervo, A.M. Chaperone-mediated autophagy and endosomal microautophagy: Joint by a chaperone. J. Biol. Chem., 2018, 293(15), 5414-5424.
[] [PMID: 29247007]
Caballero, B.; Bourdenx, M.; Luengo, E.; Diaz, A.; Sohn, P.D.; Chen, X.; Wang, C.; Juste, Y.R.; Wegmann, S.; Patel, B.; Young, Z.T.; Kuo, S.Y.; Rodriguez-Navarro, J.A.; Shao, H.; Lopez, M.G.; Karch, C.M.; Goate, A.M.; Gestwicki, J.E.; Hyman, B.T.; Gan, L.; Cuervo, A.M. Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. Nat. Commun., 2021, 12(1), 2238.
[] [PMID: 33854069]
Arias, E. Methods to study Chaperone-mediated autophagy. Methods Enzymol., 2017, 588, 283-305.
[] [PMID: 28237106]
Patel, B.; Cuervo, A.M. Methods to study chaperone-mediated autophagy. Methods, 2015, 75, 133-140.
[] [PMID: 25595300]
Kaushik, S.; Cuervo, A.M. Methods to monitor chaperone-mediated autophagy. Methods Enzymol., 2009, 452, 297-324.
[] [PMID: 19200890]
Pajares, M.; Rojo, A.I.; Arias, E.; Díaz-Carretero, A.; Cuervo, A.M.; Cuadrado, A. Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A. Autophagy, 2018, 14(8), 1310-1322.
[] [PMID: 29950142]
Cuervo, A.M.; Stefanis, L.; Fredenburg, R.; Lansbury, P.T.; Sulzer, D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science, 2004, 305(5688), 1292-1295.
[] [PMID: 15333840]
Koga, H.; Martinez-Vicente, M.; Macian, F.; Verkhusha, V.V.; Cuervo, A.M. A photoconvertible fluorescent reporter to track chaperone-mediated autophagy. Nat. Commun., 2011, 2(1), 386.
[] [PMID: 21750540]
Xu, X.; Sun, Y.; Cen, X.; Shan, B.; Zhao, Q.; Xie, T.; Wang, Z.; Hou, T.; Xue, Y.; Zhang, M.; Peng, D.; Sun, Q.; Yi, C.; Najafov, A.; Xia, H. Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model. Protein Cell, 2021, 12(10), 769-787.
[] [PMID: 34291435]
Oshima, M.; Seki, T.; Kurauchi, Y.; Hisatsune, A.; Katsuki, H. Reciprocal regulation of Chaperone-mediated autophagy/microautophagy and exosome release. Biol. Pharm. Bull., 2019, 42(8), 1394-1401.
[] [PMID: 31366874]
Xue, N.; Lai, F.; Du, T.; Ji, M.; Liu, D.; Yan, C.; Zhang, S.; Yu, X.; Jin, J.; Chen, X. Chaperone-mediated autophagy degradation of IGF-1Rβ induced by NVP-AUY922 in pancreatic cancer. Cell. Mol. Life Sci., 2019, 76(17), 3433-3447.
[] [PMID: 30980109]
Allende-Vega, N.; Villalba, M. Metabolic stress controls mutant p53 R248Q stability in acute myeloid leukemia cells. Sci. Rep., 2019, 9(1), 5637.
[] [PMID: 30948782]
Finn, P.F.; Mesires, N.T.; Vine, M.; Dice, J.F. Effects of small molecules on chaperone-mediated autophagy. Autophagy, 2005, 1(3), 141-145.
[] [PMID: 16874031]
Anguiano, J.; Garner, T.P.; Mahalingam, M.; Das, B.C.; Gavathiotis, E.; Cuervo, A.M. Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives. Nat. Chem. Biol., 2013, 9(6), 374-382.
[] [PMID: 23584676]
Ouchida, A.T.; Li, Y.; Geng, J.; Najafov, A.; Ofengeim, D.; Sun, X.; Yu, Q.; Yuan, J. Synergistic effect of a novel autophagy inhibitor and quizartinib enhances cancer cell death. Cell Death Dis., 2018, 9(2), 138.
[] [PMID: 29374185]
Sato, M.; Ueda, E.; Konno, A.; Hirai, H.; Kurauchi, Y.; Hisatsune, A.; Katsuki, H.; Seki, T. Glucocorticoids negatively regulates chaperone mediated autophagy and microautophagy. Biochem. Biophys. Res. Commun., 2020, 528(1), 199-205.
[] [PMID: 32487317]
Macri, C.; Wang, F.; Tasset, I.; Schall, N.; Page, N.; Briand, J.P.; Cuervo, A.M.; Muller, S. Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide. Autophagy, 2015, 11(3), 472-486.
[] [PMID: 25719862]
Wing, S.S.; Chiang, H.L.; Goldberg, A.L.; Dice, J.F. Proteins containing peptide sequences related to Lys-Phe-Glu-Arg-Gln are selectively depleted in liver and heart, but not skeletal muscle, of fasted rats. Biochem. J., 1991, 275(Pt 1), 165-169.
[] [PMID: 2018472]
Tasset, I.; Cuervo, A.M. Role of chaperone-mediated autophagy in metabolism. FEBS J., 2016, 283(13), 2403-2413.
[] [PMID: 26854402]
Singh, R.; Kaushik, S.; Wang, Y.; Xiang, Y.; Novak, I.; Komatsu, M.; Tanaka, K.; Cuervo, A.M.; Czaja, M.J. Autophagy regulates lipid metabolism. Nature, 2009, 458(7242), 1131-1135.
[] [PMID: 19339967]
Rodriguez-Navarro, J.A.; Kaushik, S.; Koga, H.; Dall’Armi, C.; Shui, G.; Wenk, M.R.; Di Paolo, G.; Cuervo, A.M. Inhibitory effect of dietary lipids on chaperone-mediated autophagy. Proc. Natl. Acad. Sci. USA, 2012, 109(12), E705-E714.
[] [PMID: 22331875]
Cuervo, A.M.; Terlecky, S.R.; Dice, J.F.; Knecht, E. Selective binding and uptake of ribonuclease A and glyceraldehyde-3-phosphate dehydrogenase by isolated rat liver lysosomes. J. Biol. Chem., 1994, 269(42), 26374-26380.
[] [PMID: 7929357]
Kon, M.; Kiffin, R.; Koga, H.; Chapochnick, J.; Macian, F.; Varticovski, L.; Cuervo, A.M. Chaperone-mediated autophagy is required for tumor growth. Sci. Transl. Med., 2011, 3(109), 109ra117.
[] [PMID: 22089453]
Schneider, J.L.; Suh, Y.; Cuervo, A.M. Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab., 2014, 20(3), 417-432.
[] [PMID: 25043815]
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. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol. Cell, 2011, 42(6), 719-730.
[] [PMID: 21700219]
Pastorino, J.G.; Hoek, J.B.; Hexokinase, I.I. Hexokinase II: The integration of energy metabolism and control of apoptosis. Curr. Med. Chem., 2003, 10(16), 1535-1551.
[] [PMID: 12871125]
Xia, H.G.; Najafov, A.; Geng, J.; Galan-Acosta, L.; Han, X.; Guo, Y.; Shan, B.; Zhang, Y.; Norberg, E.; Zhang, T.; Pan, L.; Liu, J.; Coloff, J.L.; Ofengeim, D.; Zhu, H.; Wu, K.; Cai, Y.; Yates, J.R.; Zhu, Z.; Yuan, J.; Vakifahmetoglu-Norberg, H. Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death. J. Cell Biol., 2015, 210(5), 705-716.
[] [PMID: 26323688]
Balmer, D.; Emery, M.; Andreux, P.; Auwerx, J.; Ginet, V.; Puyal, J.; Schorderet, D.F.; Roduit, R. Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells. PLoS One, 2013, 8(9), e74162.
[] [PMID: 24066113]
Su, K.; Yi, B.; Yao, B.Q.; Xia, T.; Yang, Y.F.; Zhang, Z.H.; Chen, C. Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis. Pharmacol. Res., 2020, 156, 104778.
[] [PMID: 32247822]
Trampel, D.W.; Sell, J.L.; Ahn, D.U.; Sebranek, J.G. Preharvest feed withdrawal affects liver lipid and liver color in broiler chickens. Poult. Sci., 2005, 84(1), 137-142.
[] [PMID: 15685953]
Cejas, J.R.; Almansa, E.; Jérez, S.; Bolaños, A.; Samper, M.; Lorenzo, A. Lipid and fatty acid composition of muscle and liver from wild and captive mature female broodstocks of white seabream, Diplodus sargus. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2004, 138(1), 91-102.
[] [PMID: 15142540]
Qiao, L.; Wang, H.F.; Xiang, L.; Ma, J.; Zhu, Q.; Xu, D.; Zheng, H.; Peng, J.Q.; Zhang, S.; Lu, H.X.; Chen, W.Q.; Zhang, Y. Deficient Chaperone-mediated autophagy promotes lipid accumulation in macrophage. J. Cardiovasc. Transl. Res., 2021, 14(4), 661-669.
[] [PMID: 32285315]
Tsai, T.H.; Chen, E.; Li, L.; Saha, P.; Lee, H.J.; Huang, L.S.; Shelness, G.S.; Chan, L.; Chang, B.H. The constitutive lipid droplet protein PLIN2 regulates autophagy in liver. Autophagy, 2017, 13(7), 1130-1144.
[] [PMID: 28548876]
Zhou, L.; Song, Z.; Hu, J.; Liu, L.; Hou, Y.; Zhang, X.; Yang, X.; Chen, K. ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3. Theranostics, 2021, 11(2), 841-860.
[] [PMID: 33391508]
Kaushik, S.; Cuervo, A.M. Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nat. Cell Biol., 2015, 17(6), 759-770.
[] [PMID: 25961502]
Endicott, S.J.; Monovich, A.C.; Huang, E.L.; Henry, E.I.; Boynton, D.N.; Beckmann, L.J.; MacCoss, M.J.; Miller, R.A. Lysosomal targetomics of ghr KO mice shows Chaperone-mediated autophagy degrades nucleocytosolic acetyl-coA enzymes. Autophagy, 2021, 2021, 1990670.
[] [PMID: 34704522]
Portovedo, M.; Reginato, A.; Miyamoto, J.E.; Simino, L.A.; Hakim, M.P.; Campana, M.; Leal, R.F.; Ignácio-Souza, L.M.; Torsoni, M.A.; Magnan, C.; Le Stunff, H.; Torsoni, A.S.; Milanski, M. Lipid excess affects Chaperone-mediated autophagy in hypothalamus. Biochimie, 2020, 176, 110-116.
[] [PMID: 32623049]
Suzuki, A.; Iwata, J. Amino acid metabolism and autophagy in skeletal development and homeostasis. Bone, 2021, 146, 115881.
[] [PMID: 33578033]
Hildebrandt, T.M.; Nunes Nesi, A.; Araújo, W.L.; Braun, H.P. Amino acid catabolism in plants. Mol. Plant, 2015, 8(11), 1563-1579.
[] [PMID: 26384576]
Jäger, R.; Kerksick, C.M.; Campbell, B.I.; Cribb, P.J.; Wells, S.D.; Skwiat, T.M.; Purpura, M.; Ziegenfuss, T.N.; Ferrando, A.A.; Arent, S.M.; Smith-Ryan, A.E.; Stout, J.R.; Arciero, P.J.; Ormsbee, M.J.; Taylor, L.W.; Wilborn, C.D.; Kalman, D.S.; Kreider, R.B.; Willoughby, D.S.; Hoffman, J.R.; Krzykowski, J.L.; Antonio, J. International society of sports nutrition position stand: Protein and exercise. J. Int. Soc. Sports Nutr., 2017, 14(1), 20.
[] [PMID: 28642676]
Muhammad, N.; Lee, H.M.; Kim, J. Oncology therapeutics targeting the metabolism of amino acids. Cells, 2020, 9(8), 1904.
Bejarano, E.; Rodríguez-Navarro, J.A. Autophagy and amino acid metabolism in the brain: Implications for epilepsy. Amino Acids, 2015, 47(10), 2113-2126.
[] [PMID: 25145921]
Nicklin, P.; Bergman, P.; Zhang, B.; Triantafellow, E.; Wang, H.; Nyfeler, B.; Yang, H.; Hild, M.; Kung, C.; Wilson, C.; Myer, V.E.; MacKeigan, J.P.; Porter, J.A.; Wang, Y.K.; Cantley, L.C.; Finan, P.M.; Murphy, L.O. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell, 2009, 136(3), 521-534.
[] [PMID: 19203585]
Wei, Z.; Liu, X.; Cheng, C.; Yu, W.; Yi, P. Metabolism of amino acids in cancer. Front. Cell Dev. Biol., 2021, 8, 603837.
[] [PMID: 33511116]
Han, J.M.; Jeong, S.J.; Park, M.C.; Kim, G.; Kwon, N.H.; Kim, H.K.; Ha, S.H.; Ryu, S.H.; Kim, S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell, 2012, 149(2), 410-424.
[] [PMID: 22424946]
Demetriades, C.; Doumpas, N.; Teleman, A.A. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell, 2014, 156(4), 786-799.
[] [PMID: 24529380]
Yang, M.; Han, Y.; Luo, S.; Xiong, X.; Zhu, X.; Zhao, H.; Jiang, N.; Xiao, Y.; Wei, L.; Li, C.; Yang, J.; Sun, L. MAMs protect against ectopic fat deposition and lipid-related kidney damage in DN patients. Front. Endocrinol. (Lausanne), 2021, 12, 609580.
[] [PMID: 33679616]
Zhang, Z.; Ni, L.; Zhang, L.; Zha, D.; Hu, C.; Zhang, L.; Feng, H.; Wei, X.; Wu, X. Empagliflozin regulates the AdipoR1/p-AMPK/p-ACC pathway to alleviate lipid deposition in diabetic nephropathy. Diabetes Metab. Syndr. Obes., 2021, 14, 227-240.
[] [PMID: 33500643]
Chen, X.; Han, Y.; Gao, P.; Yang, M.; Xiao, L.; Xiong, X.; Zhao, H.; Tang, C.; Chen, G.; Zhu, X.; Yuan, S.; Liu, F.; Dong, L.Q.; Liu, F.; Kanwar, Y.S.; Sun, L. Disulfide-bond a oxidoreductase-like protein protects against ectopic fat deposition and lipid-related kidney damage in diabetic nephropathy. Kidney Int., 2019, 95(4), 880-895.
[] [PMID: 30791996]
Sooparb, S.; Price, S.R.; Shaoguang, J.; Franch, H.A. Suppression of chaperone-mediated autophagy in the renal cortex during acute diabetes mellitus. Kidney Int., 2004, 65(6), 2135-2144.
[] [PMID: 15149326]
Luo, Y.; Wu, M.Y.; Deng, B.Q.; Huang, J.; Hwang, S.H.; Li, M.Y.; Zhou, C.Y.; Zhang, Q.Y.; Yu, H.B.; Zhao, D.K.; Zhang, G.; Qin, L.; Peng, A.; Hammock, B.D.; Liu, J.Y. Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK. Proc. Natl. Acad. Sci. USA, 2019, 116(11), 5154-5159.
[] [PMID: 30804206]
Sun, W.; Liu, C.; Chen, Q.; Liu, N.; Yan, Y.; Liu, B. SIRT3: A new regulator of cardiovascular diseases. Oxid. Med. Cell. Longev., 2018, 2018, 7293861.
[] [PMID: 29643974]
Salvatori, I.; Valle, C.; Ferri, A.; Carrì, M.T. SIRT3 and mitochondrial metabolism in neurodegenerative diseases. Neurochem. Int., 2017, 109, 184-192.
[] [PMID: 28449871]
Yi, X.; Guo, W.; Shi, Q.; Yang, Y.; Zhang, W.; Chen, X.; Kang, P.; Chen, J.; Cui, T.; Ma, J.; Wang, H.; Guo, S.; Chang, Y.; Liu, L.; Jian, Z.; Wang, L.; Xiao, Q.; Li, S.; Gao, T.; Li, C. SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative Stress-Induced melanocyte degeneration in vitiligo. Theranostics, 2019, 9(6), 1614-1633.
[] [PMID: 31037127]
Hirschey, M.D.; Shimazu, T.; Goetzman, E.; Jing, E.; Schwer, B.; Lombard, D.B.; Grueter, C.A.; Harris, C.; Biddinger, S.; Ilkayeva, O.R.; Stevens, R.D.; Li, Y.; Saha, A.K.; Ruderman, N.B.; Bain, J.R.; Newgard, C.B.; Farese, R.V., Jr; Alt, F.W.; Kahn, C.R.; Verdin, E. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 2010, 464(7285), 121-125.
[] [PMID: 20203611]
Zhang, T.; Liu, J.; Shen, S.; Tong, Q.; Ma, X.; Lin, L. SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity. Cell Death Differ., 2020, 27(1), 329-344.
[] [PMID: 31160717]
Ma, S.Y.; Sun, K.S.; Zhang, M.; Zhou, X.; Zheng, X.H.; Tian, S.Y.; Liu, Y.S.; Chen, L.; Gao, X.; Ye, J.; Zhou, X.M.; Wang, J.B.; Han, Y. Disruption of Plin5 degradation by CMA causes lipid homeostasis imbalance in NAFLD. Liver Int., 2020, 40(10), 2427-2438.
[] [PMID: 32339374]
Angelini, G.; Castagneto Gissey, L.; Del Corpo, G.; Giordano, C.; Cerbelli, B.; Severino, A.; Manco, M.; Basso, N.; Birkenfeld, A.L.; Bornstein, S.R.; Genco, A.; Mingrone, G.; Casella, G. New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery. Sci. Rep., 2019, 9(1), 17315.
[] [PMID: 31754142]
You, Y.; Li, W.Z.; Zhang, S.; Hu, B.; Li, Y.X.; Li, H.D.; Tang, H.H.; Li, Q.W.; Guan, Y.Y.; Liu, L.X.; Bao, W.L.; Shen, X. SNX10 mediates alcohol-induced liver injury and steatosis by regulating the activation of chaperone-mediated autophagy. J. Hepatol., 2018, 69(1), 129-141.
[] [PMID: 29452206]
Wu, H.; Chen, S.; Ammar, A.B.; Xu, J.; Wu, Q.; Pan, K.; Zhang, J.; Hong, Y. Crosstalk between macroautophagy and Chaperone-mediated autophagy: Implications for the treatment of neurological diseases. Mol. Neurobiol., 2015, 52(3), 1284-1296.
[] [PMID: 25330936]
Ho, P.W.; Leung, C.T.; Liu, H.; Pang, S.Y.; Lam, C.S.; Xian, J.; Li, L.; Kung, M.H.; Ramsden, D.B.; Ho, S.L. Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: Role for therapeutic activation of chaperone-mediated autophagy (CMA). Autophagy, 2020, 16(2), 347-370.
[] [PMID: 30983487]
Rios, J.; Sequeida, A.; Albornoz, A.; Budini, M. Chaperone mediated autophagy substrates and components in cancer. Front. Oncol., 2021, 10, 614677.
[] [PMID: 33643916]
Gómez-Sintes, R.; Arias, E. Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration. Mol. Aspects Med., 2021, 82, 101025.
[] [PMID: 34629183]
Hou, T.; Fan, Y.; Dan, W.; Liu, B.; Wang, Z.; Zeng, J.; Li, L. Chaperone-mediated autophagy in cancer: Advances from bench to bedside. Histol. Histopathol., 2020, 35(7), 637-644.
[PMID: 31965560]
Cuervo, A.M.; Wong, E. Chaperone-mediated autophagy: Roles in disease and aging. Cell Res., 2014, 24(1), 92-104.
[] [PMID: 24281265]
Auzmendi-Iriarte, J.; Matheu, A. Impact of Chaperone-mediated autophagy in brain aging: Neurodegenerative diseases and glioblastoma. Front. Aging Neurosci., 2021, 12, 630743.
[] [PMID: 33633561]
Massey, A.C.; Zhang, C.; Cuervo, A.M. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol., 2006, 73, 205-235.
[] [PMID: 16782460]
Zhang, Y.; Sowers, J.R.; Ren, J. Targeting autophagy in obesity: From pathophysiology to management. Nat. Rev. Endocrinol., 2018, 14(6), 356-376.
[] [PMID: 29686432]
Tan, Y.; Gong, Y.; Dong, M.; Pei, Z.; Ren, J. Role of autophagy in inherited metabolic and endocrine myopathies. Biochim. Biophys. Acta Mol. Basis Dis., 2019, 1865(1), 48-55.
[] [PMID: 30343140]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy