Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism
Mostafa Zamani, Jennifer Taher, Khosrow Adeli
Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism
Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism (known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100 (apoB100), the structural protein component of very low-density lipoproteins (VLDLs), and further targets lipid droplets (LDs), the cellular storage for neutral lipids. Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.
autophagy / lipophagy / lipid droplets / apolipoprotein B-100 / VLDL / dyslipidemia / hepatic steatosis
[1] |
Ashford TP, Porter KR. Cytoplasmic components in hepat-ic cell lysosomes[J]. J Cell Biol, 1962,12(1):198–202.
|
[2] |
Klionsky DJ. Autophagy revisited: a conversation with Christian de Duve[J]. Autophagy, 2008,4(6):740–743.
|
[3] |
Jaber N, Dou Z, Chen J-S ,
|
[4] |
Funderburk SF, Wang QJ, Yue Z . The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond[J]. Trends Cell Biol, 2010,20(6):355–362.
|
[5] |
[Romanov J, Walczak M, Ibiricu I ,
|
[6] |
Glick D, Barth S, Macleod KF . Autophagy: cellular and molecular mechanisms[J]. J Pathol, 2010,221(1):3–12.
|
[7] |
Youle RJ, Narendra DP. Mechanisms of mitophagy[J]. Nat Rev Mol Cell Biol, 2011,12(1):9–14.
|
[8] |
Mizushima N. The pleiotropic role of autophagy: from protein metabolism to bactericide[J]. Cell Death Differ, 2005,12:1535–1541.
|
[9] |
Listenberger LL, Han X, Lewis SE ,
|
[10] |
Zehmer JK, Huang Y, Peng G ,
|
[11] |
Gubern A, Barceló-Torns M, Casas J ,
|
[12] |
Schaffer JE. Lipotoxicity: when tissues overeat[J]. Curr Opin Lipidol, 2003,14(3):281–287.
|
[13] |
Gibbons GF, Wiggins D. Intracellular triacylglycerol lipase: its role in the assembly of hepatic very-low-density lipoprotein (VLDL)[J]. Adv Biol Regul, 1995,35:179–198.
|
[14] |
Ye J, Li JZ, Liu Y ,
|
[15] |
Ohsaki Y, Cheng J,Fujita A ,
|
[16] |
Ohsaki Y, Cheng J, Suzuki M ,
|
[17] |
Wu JW, Wang SP, Alvarez F ,
|
[18] |
Reid BN, Ables GP, Otlivanchik OA ,
|
[19] |
Lehner R, Verger R. Purification and characterization of a porcine liver microsomal triacylglycerol hydrolase[J]. Biochemistry, 1997,36(7):1861–1868.
|
[20] |
Lehner R, Vance D. Cloning and expression of a cDNA encoding a hepatic microsomal lipase that mobilizes stored triacylglycerol[J]. Biochem J, 1999,343:1–10.
|
[21] |
Gilham D, Alam M, Gao W ,
|
[22] |
Lehner R, Cui Z, Vance D . Subcellullar localization, developmental expression and characterization of a liv-er triacylglycerol hydrolase[J]. Biochem J, 1999,338: 761–768.
|
[23] |
Rustan AC, Nossen JO, Tefre T ,
|
[24] |
Nossen JO, Rustan AC, Barnard T ,
|
[25] |
Du H, Heur M, Duanmu M ,
|
[26] |
Brown MS, Goldstein JL. Receptor-mediated control of cholesterol metabolism[J]. Science, 1976,191(4223): 150–154.
|
[27] |
Singh R, Kaushik S, Wang Y ,
|
[28] |
Neufeld TP. TOR-dependent control of autophagy: biting the hand that feeds[J]. Curr Opin Cell Biol, 2010,22(2): 157–168.
|
[29] |
Dikic I, Johansen T, Kirkin V . Selective autophagy in can-cer development and therapy[J]. Cancer Res, 2010,70(9): 3431–3434.
|
[30] |
Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins[J]. Autophagy, 2011,7(3): 279–296.
|
[31] |
Fujimoto Y, Itabe H, Sakai J ,
|
[32] |
Okumura T. Role of lipid droplet proteins in liver steato-sis[J]. J Physiol Biochem, 2011,67(4):629–636.
|
[33] |
Bickel PE, Tansey JT, Welte MA . PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores[J]. Biochim Biophys Acta, 2009,1791(6):419–440.
|
[34] |
Dong H, Czaja MJ. Regulation of lipid droplets by auto-phagy[J]. Trends Endocrinol Metab, 2011,22(6):234–240.
|
[35] |
Spandl J, Lohmann D, Kuerschner L ,
|
[36] |
Rutledge AC, Su Q, Adeli K . Apolipoprotein B100 biogen-esis: a complex array of intracellular mechanisms regulating folding, stability, and lipoprotein assembly[J]. Biochem Cell Biol, 2010,88(2):251–267.
|
[37] |
Hussain MM, Shi J, Dreizen P . Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly[J]. J Lipid Res, 2003,44(1):22–32.
|
[38] |
Liao W, Chang BHJ, Mancini M ,
|
[39] |
Pan M, Cederbaum AI, Zhang Y-L ,
|
[40] |
Andreo U, Guo L, Chirieac DV ,
|
[41] |
Fisher EA, Pan M, Chen X ,
|
[42] |
Qiu W, Kohen-Avramoglu R, Mhapsekar S ,
|
[43] |
Zhong S, Magnolo AL, Sundaram M ,
|
[44] |
Bostr�m K, Boren J, Wettesten M ,
|
[45] |
Sparks JD, O'Dell C, Chamberlain JM ,
|
[46] |
Chamberlain JM, O’Dell C, Sparks CE ,
|
[47] |
Gustafsen C, Kjolby M, Nyegaard M ,
|
[48] |
Norata GD, Tibolla G, Catapano AL . Targeting PCSK9 for hypercholesterolemia[J]. Annu Rev Pharmacol Toxicol, 2014,54:273–293.
|
[49] |
Sun H, Samarghandi A, Zhang N ,
|
[50] |
Grattagliano I, Portincasa P, Palmieri VO ,
|
[51] |
Yang L, Li P, Fu S ,
|
[52] |
Gonzalez-Rodriguez A , Mayoral R , Agra N,
|
[53] |
Francone OL, Kalopissis AD, Griffaton G . Contribution of cytoplasmic storage triacylglycerol to VLDL-triacylglycerol in isolated rat hepatocytes[J]. Biochim Biophys Acta, 1989,1002(1):28–36.
|
[54] |
Škop V, Cahová M, Papáčková Z,
|
[55] |
Kasiske BL, De Mattos A, Flechner SM ,
|
[56] |
Adeli K, Taghibiglou C, Van Iderstine SC,
|
[57] |
Festi D, Colecchia A, Sacco T ,
|
[58] |
Flamment M, Hajduch E, Ferré P ,
|
[59] |
Khamzina L, Veilleux A, Bergeron S ,
|
[60] |
Liu H-Y, Han J, Cao SY ,
|
[61] |
Mells JE, Fu PP, Sharma S ,
|
[62] |
Taher J, Baker CL, Cuizon C ,
|
[63] |
Farr S, Taher J, Adeli K . Glucagon-like peptide-1 as a key regulator of lipid and lipoprotein metabolism in fasting and postprandial states[J]. Cardiovasc Hematol Disord Drug Targets, 2014,14(2):126–136.
|
[64] |
Parlevliet ET, Wang Y, Geerling JJ ,
|
[65] |
Sharma S, Mells JE, Fu PP ,
|
[66] |
Christian P, Sacco J, Adeli K . Autophagy: emerging roles in lipid homeostasis and metabolic control. Biochim Biophys Acta, 2013,1831(4):819–824.
|
/
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