Mitochondrial cholesterol accumulation in alcoholic liver disease: Role of ASMase and endoplasmic reticulum stress

Redox Biology

Volumn 3, Issue , 2014, Pages 100-108

  Marí, Montserrat ^a   Morales, Albert ^a   Colell, Anna ^a   García Ruiz, Carmen ^a   Fernández Checa, Jose C ^a,b  

^a INST D INVESTIGACIONS B   (Spain)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Acid sphingomyelinase; ER stress; Lipotoxicity; Mitochondrial cholesterol; Mitochondrial GSH; Mitochondrial respiratory chain

Indexed keywords

ALCOHOL; GLUTATHIONE; HYPOXIA INDUCIBLE FACTOR 1; REACTIVE OXYGEN METABOLITE; SPHINGOMYELIN PHOSPHODIESTERASE; STEROIDOGENIC ACUTE REGULATORY PROTEIN; CHOLESTEROL;

AEROBIC METABOLISM; ALCOHOL CONSUMPTION; ALCOHOL LIVER DISEASE; ARTICLE; CELL FUNCTION; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; CHOLESTEROL TRANSPORT; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN REGULATION; ENDOPLASMIC RETICULUM STRESS; GLYCOLYSIS; INTRACELLULAR TRANSPORT; LACTATE SECRETION; METABOLIC REGULATION; METABOLIC REPROGRAMMING; MITOCHONDRIAL CHOLESTEROL ACCUMULATION; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; REGULATORY MECHANISM; SECRETION (PROCESS); UPREGULATION; ANIMAL; HUMAN; LIVER MITOCHONDRION; METABOLISM;

ANIMALS; CHOLESTEROL; ENDOPLASMIC RETICULUM STRESS; GLUTATHIONE; HUMANS; LIVER DISEASES, ALCOHOLIC; MITOCHONDRIA, LIVER; REACTIVE OXYGEN SPECIES; SPHINGOMYELIN PHOSPHODIESTERASE;

EID: 84918532861     PISSN: 22132317     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.redox.2014.09.005     Document Type: Article

References (116)

1. O'Shea R.S., Dasarathy S., McCullough A.J. Alcoholic liver disease. Hepatology 2010, 51:307-328. Practice Guideline Committee of the American Association for the Study of Liver Disease and Practice Parameters Committee of the American College of Gastroenterology. 10.1002/hep.23258.
2. Beckett A.G., Livingstone A.V., Hill K.R. Acute alcoholic hepatitis. Br. Med. J. 1961, 2:1113-1119. http://www.ncbi.nlm.nih.gov/pubmed/13866411, 10.1136/bmj.2.5260.1113.
3. Lefkowitch J.H. Morphology of alcoholic liver disease. Clin. Liver Dis. 2005, 9:37-53. http://www.ncbi.nlm.nih.gov/pubmed/15763228, 10.1016/j.cld.2004.11.001.
4. Méndez-Sánchez N., Almeda-Valdés P., Uribe M. Alcoholic liver disease. An update. Ann. Hepatol. 2005, 4:32-42. http://www.ncbi.nlm.nih.gov/pubmed/15798659.
5. MacSween R.N., Burt A.D. Histologic spectrum of alcoholic liver disease. Semin. Liver Dis. 1986, 6:221-232. http://www.ncbi.nlm.nih.gov/pubmed/3022386, 10.1055/s-2008-1040605.
6. Frazier T.H., Stocker A.M., Kershner N.A., Marsano L.S., McClain C.J. Treatment of alcoholic liver disease. Ther. Adv. Gastroenterol. 2011, 4:63-81. http://www.ncbi.nlm.nih.gov/pubmed/21317995, 10.1177/1756283X10378925.
7. García-Ruiz C., Kaplowitz N., Fernandez-Checa J.C. Role of mitochondria in alcoholic Liver disease. Curr. Pathobiol. Rep. 2013, 1:159-168. 10.1007/s40139-013-0021-z.
8. Fernández A., Colell A., Garcia-Ruiz C., Fernandez-Checa J.C. Cholesterol and sphingolipids in alcohol-induced liver injury. J. Gastroenterol. Hepatol. 2008, 23(Suppl. 1):S9-15. http://www.ncbi.nlm.nih.gov/pubmed/18336673, 10.1111/j.1440-1746.2007.05280.x.
9. Brunt E.M. Alcoholic and nonalcoholic steatohepatitis. Clin. Liver Dis. 2002, 6:399-420. http://www.ncbi.nlm.nih.gov/pubmed/12122863, 10.1016/S1089-3261(02)00002-8.
10. Garcia-Ruiz C., Mato J.M., Vance D., Kaplowitz N., Fernandez-Checa J.C. The acid sphingomyelinase-ceramide system in steatohepatitis. A novel target regulating multiple pathways. J. Hepatol. 2014, In press.
11. Nassir F., ah J.A. Role of mitochondria in alcoholic liver disease. World J. Gastroenterol. 2014, 20:2136-2142. http://www.ncbi.nlm.nih.gov/pubmed/24605012, 10.3748/wjg.v20.i9.2136.
12. Cheng Z., Ristow M. Mitochondria and metabolic homeostasis. Antioxid. Redox Signal. 2013, 19:240-242. http://www.ncbi.nlm.nih.gov/pubmed/23432475, 10.1089/ars.2013.5255.
13. Hamanaka R.B., Chandel N.S. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem. Sci. 2010, 35:505-513. http://www.ncbi.nlm.nih.gov/pubmed/20430626, 10.1016/j.tibs.2010.04.002.
14. Murphy M.P. How mitochondria produce reactive oxygen species. Biochem. J. 2009, 417:1-13. http://www.ncbi.nlm.nih.gov/pubmed/19061483, 10.1042/BJ20081386.
15. Marí M., Colell A., Morales A., von Montfort C., Garcia-Ruiz C., Fernández-Checa J.C. Redox control of liver function in health and disease. Antioxid. Redox Signal. 2010, 12:1295-1331. http://www.ncbi.nlm.nih.gov/pubmed/19803748, 10.1089/ars.2009.2634.
16. Wallace D.C., Fan W., Procaccio V. Mitochondrial energetics and therapeutics. Annu. Rev. Pathol. 2010, 5:297-348. http://www.ncbi.nlm.nih.gov/pubmed/20078222, 10.1146/annurev.pathol.4.110807.092314.
17. Marí M., Morales A., Colell A., García-Ruiz C., Fernández-Checa J.C. Mitochondrial glutathione, a key survival antioxidant. Antioxid. Redox Signal. 2009, 11:2685-2700. http://www.ncbi.nlm.nih.gov/pubmed/19558212, 10.1089/ARS.2009.2695.
18. Degli Esposti D., Hamelin J., Bosselut N., Saffroy R., Sebagh M., Pommier A., et al. Mitochondrial roles and cytoprotection in chronic liver injury. Biochem. Res. Int. 2012, 2012:387626. http://www.ncbi.nlm.nih.gov/pubmed/22745910, 10.1155/2012/387626.
19. Hoek J.B., Cahill A., Pastorino J.G. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterology 2002, 122:2049-2063. http://www.ncbi.nlm.nih.gov/pubmed/12055609, 10.1053/gast.2002.33613.
20. Ribas V., García-Ruiz C., Fernández-Checa J.C. Glutathione and mitochondria. Front. Pharmacol. 2014, 5:151. http://www.ncbi.nlm.nih.gov/pubmed/25024695, 10.3389/fphar.2014.00151.
21. Tait S.W., Green D.R. Mitochondria and cell signalling. J. Cell Sci. 2012, 125:807-815. http://www.ncbi.nlm.nih.gov/pubmed/22448037, 10.1242/jcs.099234.
22. Rector R.S., Thyfault J.P., Uptergrove G.M., Morris E.M., Naples S.P., Borengasser S.J., et al. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J. Hepatol. 2010, 52:727-736. http://www.ncbi.nlm.nih.gov/pubmed/20347174, 10.1016/j.jhep.2009.11.030.
23. Lemasters J.J. Variants of mitochondrial autophagy: types 1 and 2 mitophagy and micromitophagy (type 3). Redox Biol. 2014, 2:749-754. http://www.ncbi.nlm.nih.gov/pubmed/25009776, 10.1016/j.redox.2014.06.004.
24. Bruguera M., Bertran A., Bombi J.A., Rodes J. Giant mitochondria in hepatocytes: a diagnostic hint for alcoholic liver disease. Gastroenterology 1977, 73:1383-1387. http://www.ncbi.nlm.nih.gov/pubmed/913978.
25. Chedid A., Mendenhall C.L., Tosch T., Chen T., Rabin L., Garcia-Pont P., et al. Significance of megamitochondria in alcoholic liver disease. Gastroenterology 1986, 90:1858-1864. http://www.ncbi.nlm.nih.gov/pubmed/3699404.
26. Fromenty B., Grimbert S., Mansouri A., Beaugrand M., Erlinger S., Rötig A., et al. Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis. Gastroenterology 1995, 108:193-200. http://www.ncbi.nlm.nih.gov/pubmed/7806041.
27. Rubin E., Beattie D.S., Lieber C.S. Effects of ethanol on the biogenesis of mitochondrial membranes and associated mitochondrial functions. Lab. Investig. 1970, 23:620-627. http://www.ncbi.nlm.nih.gov/pubmed/5484848.
28. Cederbaum A.I., Lieber C.S., Rubin E. Effects of chronic ethanol treatment of mitochondrial functions damage to coupling site I. Arch. Biochem. Biophys. 1974, 165:560-569. http://www.ncbi.nlm.nih.gov/pubmed/4280268.
29. Spach P.I., Cunningham C.C. Control of state 3 respiration in liver mitochondria from rats subjected to chronic ethanol consumption. Biochim. Biophys. Acta 1987, 894:460-467. http://www.ncbi.nlm.nih.gov/pubmed/2825777, 10.1016/0005-2728(87)90125-3.
30. Cunningham C.C., Coleman W.B., Spach P.I. The effects of chronic ethanol consumption on hepatic mitochondrial energy metabolism. Alcohol Alcohol. 1990, 25:127-136. http://www.ncbi.nlm.nih.gov/pubmed/2142884.
31. Cahill A., Cunningham C.C. Effects of chronic ethanol feeding on the protein composition of mitochondrial ribosomes. Electrophoresis 2000, 21:3420-3426. http://www.ncbi.nlm.nih.gov/pubmed/11079562, 10.1002/1522-2683(20001001)21:16<3420::AID-ELPS3420>3.0.CO;2-Q.
32. Venkatraman A., Landar A., Davis A.J., Chamlee L., Sanderson T., Kim H., et al. Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity. J. Biol. Chem. 2004, 279:22092-22101. http://www.ncbi.nlm.nih.gov/pubmed/15033988, 10.1074/jbc.M402245200.
33. Han D., Ybanez M.D., Johnson H.S., McDonald J.N., Mesropyan L., Sancheti H., et al. Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations. J. Biol. Chem. 2012, 287:42165-42179. http://www.ncbi.nlm.nih.gov/pubmed/23086958, 10.1074/jbc.M112.377374.
34. Cederbaum A.I. Alcohol metabolism. Clin. Liver Dis. 2012, 16:667-685. http://www.ncbi.nlm.nih.gov/pubmed/23101976, 10.1016/j.cld.2012.08.002.
35. Robin M.A., Anandatheerthavarada H.K., Fang J.K., Cudic M., Otvos L., Avadhani N.G. Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N terminus and requires mitochondrial specific electron transfer proteins for activity. J. Biol. Chem. 2001, 276:24680-24689. http://www.ncbi.nlm.nih.gov/pubmed/11325963, 10.1074/jbc.M100363200.
36. Knockaert L., Descatoire V., Vadrot N., Fromenty B., Robin M.A. Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen. Toxicol. in Vitro 2011, 25:475-484. http://www.ncbi.nlm.nih.gov/pubmed/21130154, 10.1016/j.tiv.2010.11.019.
37. Song B.J. Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 update. Alcohol. Clin. Exp. Res. 1996, 20:138A-146A. http://www.ncbi.nlm.nih.gov/pubmed/8947253.
38. Fataccioli V., Andraud E., Gentil M., French S.W., Rouach H. Effects of chronic ethanol administration on rat liver proteasome activities: relationship with oxidative stress. Hepatology 1999, 29:14-20. http://www.ncbi.nlm.nih.gov/pubmed/9862843, 10.1002/hep.510290106.
39. Sakurai K., Cederbaum A.I. Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells that express cytochrome P450 2E1. Mol. Pharmacol. 1998, 54:1024-1035. http://www.ncbi.nlm.nih.gov/pubmed/9855631.
40. Marí M., Cederbaum A.I. CYP2E1 overexpression in HepG2 cells induces glutathione synthesis by transcriptional activation of gamma-glutamylcysteine synthetase. J. Biol. Chem. 2000, 275:15563-15571. http://www.ncbi.nlm.nih.gov/pubmed/10748080, 10.1074/jbc.M907022199.
41. Marí M., Cederbaum A.I. Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress. Hepatology 2001, 33:652-661. http://www.ncbi.nlm.nih.gov/pubmed/11230746, 10.1053/jhep.2001.22521.
42. Bai J., Cederbaum A.I. Overexpression of CYP2E1 in mitochondria sensitizes HepG2 cells to the toxicity caused by depletion of glutathione. J. Biol. Chem. 2006, 281:5128-5136. http://www.ncbi.nlm.nih.gov/pubmed/16380384, 10.1074/jbc.M510484200.
43. Bansal S., Liu C.P., Sepuri N.B., Anandatheerthavarada H.K., Selvaraj V., Hoek J., et al. Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress. J. Biol. Chem. 2010, 285:24609-24619. http://www.ncbi.nlm.nih.gov/pubmed/20529841, 10.1074/jbc.M110.121822.
44. Raza H., Prabu S.K., Robin M.A., Avadhani N.G. Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: Tissue-specific variations and roles in oxidative stress. Diabetes 2004, 53:185-194. http://www.ncbi.nlm.nih.gov/pubmed/14693714, 10.2337/diabetes.53.1.185.
45. Macmillan-Crow L.A., Cruthirds D.L. Invited review: manganese superoxide dismutase in disease. Free Radic. Res. 2001, 34:325-336. http://www.ncbi.nlm.nih.gov/pubmed/11328670, 10.1080/10715760100300281.
46. Koch O.R., De Leo M.E., Borrello S., Palombini G., Galeotti T. Ethanol treatment up-regulates the expression of mitochondrial manganese superoxide dismutase in rat liver. Biochem. Biophys. Res. Commun. 1994, 201:1356-1365. http://www.ncbi.nlm.nih.gov/pubmed/8024580, 10.1006/bbrc.1994.1853.
47. Wheeler M.D., Nakagami M., Bradford B.U., Uesugi T., Mason R.P., Connor H.D., et al. Overexpression of manganese superoxide dismutase prevents alcohol-induced liver injury in the rat. J. Biol. Chem. 2001, 276:36664-36672. http://www.ncbi.nlm.nih.gov/pubmed/11477087, 10.1074/jbc.M105352200.
48. Nanji A.A., Griniuviene B., Sadrzadeh S.M., Levitsky S., McCully J.D. Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver. J. Lipid Res. 1995, 36:736-744. http://www.ncbi.nlm.nih.gov/pubmed/7616120.
49. Degoul F., Sutton A., Mansouri A., Cepanec C., Degott C., Fromenty B., et al. Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease. Gastroenterology 2001, 120:1468-1474. http://www.ncbi.nlm.nih.gov/pubmed/11313317, 10.1053/gast.2001.24051.
50. Yant L.J., Ran Q., Rao L., Van Remmen H., Shibatani T., Belter J.G., Motta L., Richardson A., Prolla T.A. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic. Biol. Med. 2003, 34:496-502. http://www.ncbi.nlm.nih.gov/pubmed/12566075, 10.1016/S0891-5849(02)01360-6.
51. Cox A.G., Winterbourn C.C., Hampton M.B. Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem. J. 2010, 425:313-325. http://www.ncbi.nlm.nih.gov/pubmed/20025614, 10.1042/BJ20091541.
52. von Montfort C., Matias N., Fernandez A., Fucho R., Conde de la Rosa L., Martinez-Chantar M.L., et al. Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis. J. Hepatol. 2012, 57:852-859. http://www.ncbi.nlm.nih.gov/pubmed/22687340, 10.1016/j.jhep.2012.05.024.
53. Zhang H., Go Y.M., Jones D.P. Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress. Arch. Biochem. Biophys. 2007, 465:119-126. http://www.ncbi.nlm.nih.gov/pubmed/17548047, 10.1016/j.abb.2007.05.001.
54. McCommis K.S., McGee A.M., Laughlin M.H., Bowles D.K., Baines C.P. Hypercholesterolemia increases mitochondrial oxidative stress and enhances the MPT response in the porcine myocardium: beneficial effects of chronic exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011, 301:R1250-R1258. http://www.ncbi.nlm.nih.gov/pubmed/21865543, 10.1152/ajpregu.00841.2010.
55. Fernandez-Checa J.C., Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol. Appl. Pharmacol. 2005, 204:263-273. http://www.ncbi.nlm.nih.gov/pubmed/15845418, 10.1016/j.taap.2004.10.001.
56. Hirano T., Kaplowitz N., Tsukamoto H., Kamimura S., Fernandez-Checa J.C. Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats. Hepatology 1992, 16:1423-1427. http://www.ncbi.nlm.nih.gov/pubmed/1446896, 10.1002/hep.1840160619.
57. García-Ruiz C., Morales A., Ballesta A., Rodés J., Kaplowitz N., Fernández-Checa J.C. Effect of chronic ethanol feeding on glutathione and functional integrity of mitochondria in periportal and perivenous rat hepatocytes. J. Clin. Investig. 1994, 94:193-201. http://www.ncbi.nlm.nih.gov/pubmed/8040260, 10.1172/JCI117306.
58. García-Ruiz C., Morales A., Colell A., Ballesta A., Rodés J., Kaplowitz N., et al. Feeding S-adenosyl-l-methionine attenuates both ethanol-induced depletion of mitochondrial glutathione and mitochondrial dysfunction in periportal and perivenous rat hepatocytes. Hepatology 1995, 21:207-214. http://www.ncbi.nlm.nih.gov/pubmed/7806156.
59. Colell A., Coll O., García-Ruiz C., París R., Tiribelli C., Kaplowitz N., et al. Tauroursodeoxycholic acid protects hepatocytes from ethanol-fed rats against tumor necrosis factor-induced cell death by replenishing mitochondrial glutathione. Hepatology 2001, 34:964-971. http://www.ncbi.nlm.nih.gov/pubmed/11679967, 10.1053/jhep.2001.28510.
60. Zhao P., Kalhorn T.F., Slattery J.T. Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. Hepatology 2002, 36:326-335. http://www.ncbi.nlm.nih.gov/pubmed/12143040, 10.1053/jhep.2002.34943.
61. Zhao P., Slattery J.T. Effects of ethanol dose and ethanol withdrawal on rat liver mitochondrial glutathione: implication of potentiated acetaminophen toxicity in alcoholics. Drug Metab. Dispos. 2002, 30:1413-1417. http://www.ncbi.nlm.nih.gov/pubmed/12433812.
62. Varatharajalu R., Garige M., Leckey L.C., Arellanes-Robledo J., Reyes-Gordillo K., Shah R., et al. Adverse signaling of scavenger receptor class B1 and PGC1s in alcoholic Hepatosteatosis and steatohepatitis and protection by Betaine in Rat. Am. J. Pathol. 2014, 184:2035-2044. http://www.ncbi.nlm.nih.gov/pubmed/24814604, 10.1016/j.ajpath.2014.03.005.
63. Mansouri A., Tarhuni A., Larosche I., Reyl-Desmars F., Demeilliers C., Degoul F., et al. MnSOD overexpression prevents liver mitochondrial DNA depletion after an alcohol binge but worsens this effect after prolonged alcohol consumption in mice. Dig. Dis. 2010, 28:756-775. http://www.ncbi.nlm.nih.gov/pubmed/21525761, 10.1159/000324284.
64. Colell A., García-Ruiz C., Miranda M., Ardite E., Marí M., Morales A., et al. Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 1998, 115:1541-1551. http://www.ncbi.nlm.nih.gov/pubmed/9834283, 10.1016/S0016-5085(98)70034-4.
65. Marí M., Colell A., Morales A., Caballero F., Moles A., Fernández A., et al. Mechanism of mitochondrial glutathione-dependent hepatocellular susceptibility to TNF despite NF-kappaB activation. Gastroenterology 2008, 134:1507-1520. http://www.ncbi.nlm.nih.gov/pubmed/18343380, 10.1053/j.gastro.2008.01.073.
66. Petrasek J., Bala S., Csak T., Lippai D., Kodys K., Menashy V., Barrieau M., Min S.Y., Kurt-Jones E.A. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J. Clin. Investig. 2012, 122:3476-3489. http://www.ncbi.nlm.nih.gov/pubmed/22945633, 10.1172/JCI60777.
67. Zhou R., Yazdi A.S., Menu P., Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011, 469:221-224. http://www.ncbi.nlm.nih.gov/pubmed/21124315, 10.1038/nature09663.
68. Iyer S.S., He Q., Janczy J.R., Elliott E.I., Zhong Z., Olivier A.K., Sadler J.J., Knepper-Adrian V., Han R., Qiao L., Eisenbarth S.C., Nauseef W.M. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 2013, 39:311-323. http://www.ncbi.nlm.nih.gov/pubmed/23954133, 10.1016/j.immuni.2013.08.001.
69. Garcia-Ruiz C., Mari M., Colell A., Morales A., Caballero F., Montero J., Terrones O., Basañez G., Fernández-Checa J.C. Mitochondrial cholesterol in health and disease. Histol. Histopathol. 2009, 24:117-132. http://www.ncbi.nlm.nih.gov/pubmed/19012251.
70. Marí M., Caballero F., Colell A., Morales A., Caballeria J., Fernandez A., et al. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab. 2006, 4:185-198. http://www.ncbi.nlm.nih.gov/pubmed/16950136, 10.1016/j.cmet.2006.07.006.
71. Fernández A., Colell A., Caballero F., Matías N., García-Ruiz C., Fernández-Checa J.C. Mitochondrial S-adenosyl-l-methionine transport is insensitive to alcohol-mediated changes in membrane dynamics. Alcohol. Clin. Exp. Res. 2009, 33:1169-1180. http://www.ncbi.nlm.nih.gov/pubmed/19389197, 10.1111/j.1530-0277.2009.00940.x.
72. Maxfield F.R., Tabas I. Role of cholesterol and lipid organization in disease. Nature 2005, 438:612-621. http://www.ncbi.nlm.nih.gov/pubmed/16319881, 10.1038/nature04399.
73. Colell A., García-Ruiz C., Lluis J.M., Coll O., Mari M., Fernández-Checa J.C. Cholesterol impairs the adenine nucleotide translocator-mediated mitochondrial permeability transition through altered membrane fluidity. J. Biol. Chem. 2003, 278:33928-33935. http://www.ncbi.nlm.nih.gov/pubmed/12821666, 10.1074/jbc.M210943200.
74. Fernandez A., Matias N., Fucho R., Ribas V., Von Montfort C., Nuño N., et al. ASMase is required for chronic alcohol induced hepatic endoplasmic reticulum stress and mitochondrial cholesterol loading. J. Hepatol. 2013, 59:805-813. http://www.ncbi.nlm.nih.gov/pubmed/23707365, 10.1016/j.jhep.2013.05.023.
75. Josekutty J., Iqbal J., Iwawaki T., Kohno K., Hussain M.M. Microsomal triglyceride transfer protein inhibition induces endoplasmic reticulum stress and increases gene transcription via Ire1alpha/cJun to enhance plasma ALT/AST. J. Biol. Chem. 2013, 288:14372-14383. http://www.ncbi.nlm.nih.gov/pubmed/23532846, 10.1074/jbc.M113.459602.
76. Ha S.D., Park S., Han C.Y., Nguyen M.L., Kim S.O. Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating MLN64 in macrophages. Mol. Cell. Biol. 2012, 32:4846-4860. http://www.ncbi.nlm.nih.gov/pubmed/23028046, 10.1128/MCB.00494-12.
77. Coll O., Colell A., García-Ruiz C., Kaplowitz N., Fernández-Checa J.C. Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology 2003, 38:692-702. http://www.ncbi.nlm.nih.gov/pubmed/12939596, 10.1053/jhep.2003.50351.
78. Mårtensson J., Lai J.C., Meister A. High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function. Proc. Natl. Acad. Sci. U.S.A. 1990, 87:7185-7189. http://www.ncbi.nlm.nih.gov/pubmed/2402500, 10.1073/pnas.87.18.7185.
79. Lluis J.M., Colell A., García-Ruiz C., Kaplowitz N., Fernández-Checa J.C. Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress. Gastroenterology 2003, 124:708-724. http://www.ncbi.nlm.nih.gov/pubmed/12612910, 10.1053/gast.2003.50089.
80. Chen Z., Putt D.A. Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria: Further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport. Arch. Biochem. Biophys. 2000, 373:193-202. http://www.ncbi.nlm.nih.gov/pubmed/10620338, 10.1006/abbi.1999.1527.
81. Gan L.T., Van Rooyen D.M., Koina M., McCuskey R.S., Teoh N.C., Farrell G.C. Hepatocytes free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4 dependent. J. Hepatol. 2014, 10.1016/j.hep.2014.07.024.
82. Ge X., Antoine D.J., Lu Y., Arriazu E., Leung T.M., Klepper A.L., Branch A.D., Fiel M.I., Nieto N. High mobility group Box-1 (HMGB1) participates in the pathogenesis of alcoholic liver disease (ALD). J. Biol. Chem. 2014, 289:22672-22691. http://www.ncbi.nlm.nih.gov/pubmed/24928512, 10.1074/jbc.M114.552141.
83. Anavi S., Hahn-Obercyger M., Madar Z., Tirosh O. Mechanism for HIF-1 activation by cholesterol under normoxia: a redox signaling pathway for liver damage. Free Radic. Biol. Med. 2014, 71:61-69. http://www.ncbi.nlm.nih.gov/pubmed/24632196, 10.1016/j.freeradbiomed.2014.03.007.
84. Lluis J.M., Morales A., Blasco C., Colell A., Mari M., Garcia-Ruiz C., et al. Critical role of mitochondrial glutathione in the survival of hepatocytes during hypoxia. J. Biol. Chem. 2005, 280:3224-3232. http://www.ncbi.nlm.nih.gov/pubmed/15548523, 10.1074/jbc.M408244200.
85. Lluis J.M., Buricchi F., Chiarugi P., Morales A., Fernandez-Checa J.C. Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-kappaB via cSrc and oxidant-dependent cell death. Cancer Res. 2007, 67:7368-7377. http://www.ncbi.nlm.nih.gov/pubmed/17671207, 10.1158/0008-5472.CAN-07-0515.
86. Nath B., Levin I., Csak T., Petrasek J., Mueller C., Kodys K., Catalano D., Mandrekar P., Szabo G. Hepatocyte-specific hypoxia-inducible factor-1α is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice. Hepatology 2011, 53:1526-1537. http://www.ncbi.nlm.nih.gov/pubmed/21520168, 10.1002/hep.24256.
87. Kennedy B.E., Madreiter C.T., Vishnu N., Malli R., Graier W.F. Adaptations of energy metabolism associated with increased levels of mitochondrial cholesterol in Niemann-Pick type C1-deficient cells. J. Biol. Chem. 2014, 289:16278-16289. http://www.ncbi.nlm.nih.gov/pubmed/24790103, 10.1074/jbc.M114.559914.
88. Bradford B.U., O'Connell T.M., Han J., Kosyk O., Shymonyak S., Ross P.K., Winnike J., Kono H., Rusyn I. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease. Toxicol. Appl. Pharmacol. 2008, 232:236-243. 10.1016/j.taap.2008.06.022.
89. Soccio R.E., Breslow J.L. StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism. J. Biol. Chem. 2003, 278:22183-22186. http://www.ncbi.nlm.nih.gov/pubmed/12724317, 10.1074/jbc.R300003200.
90. Miller W.L. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochim. Biophys. Acta 2007, 1771:663-676. http://www.ncbi.nlm.nih.gov/pubmed/17433772, 10.1016/j.bbalip.2007.02.012.
91. Caron K.M., Soo S.C., Wetsel W.C., Stocco D.M., Clark B.J., Parker K.L. Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:11540-11545. http://www.ncbi.nlm.nih.gov/pubmed/9326645, 10.1073/pnas.94.21.11540.
92. Montero J., Morales A., Llacuna L., Lluis J.M., Terrones O., Basañez G., Antonsson B., Prieto J., García-Ruiz C., Colell A., Fernández-Checa J.C. Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma. Cancer Res. 2008, 68:5246-5256. http://www.ncbi.nlm.nih.gov/pubmed/18593925, 10.1158/0008-5472.CAN-07-6161.
93. Ji C., Kaplowitz N. ER stress: Can the liver cope?. J. Hepatol. 2006, 45:321-333. http://www.ncbi.nlm.nih.gov/pubmed/16797772, 10.1016/j.jhep.2006.06.004.
94. Ji C., Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 2003, 124:1488-1499. http://www.ncbi.nlm.nih.gov/pubmed/12730887, 10.1016/S0016-5085(03)00276-2.
95. Ozcan U., Yilmaz E., Ozcan L., Furuhashi M., Vaillancourt E., Smith R.O., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006, 313:1137-1140. http://www.ncbi.nlm.nih.gov/pubmed/16931765, 10.1126/science.1128294.
96. Soccio R.E., Adams R.M., Maxwell K.N., Breslow J.L. Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J. Biol. Chem. 2005, 280:19410-19418. http://www.ncbi.nlm.nih.gov/pubmed/15760897, 10.1074/jbc.M501778200.
97. Rodriguez-Agudo D., Calderon-Dominguez M., Medina M.A., Ren S., Gil G., Pandak W.M. ER stress increases StarD5 expression by stabilizing its mRNA and leads to relocalization of its protein from the nucleus to the membranes. J. Lipid Res. 2012, 53:2708-2715. http://www.ncbi.nlm.nih.gov/pubmed/23053693, 10.1194/jlr.M031997.
98. Yamada S., Yamaguchi T., Hosoda A., Iwawaki T., Kohno K. Regulation of human STARD4 gene expression under endoplasmic reticulum stress. Biochem. Biophys. Res. Commun. 2006, 343:1079-1085. http://www.ncbi.nlm.nih.gov/pubmed/16579971, 10.1016/j.bbrc.2006.03.051.
99. Manna P.R., Soh J.W., Stocco D.M. The involvement of specific PKC isoenzymes in phorbol ester-mediated regulation of steroidogenic acute regulatory protein expression and steroid synthesis in mouse Leydig cells. Endocrinology 2011, 152:313-325. http://www.ncbi.nlm.nih.gov/pubmed/21047949, 10.1210/en.2010-0874.
100. Arakane F., King S.R., Du Y., Kallen C.B., Walsh L.P., Watari H., Stocco D.M., Strauss J.F. Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity. J. Biol. Chem. 1997, 272:32656-32662. http://www.ncbi.nlm.nih.gov/pubmed/9405483, 10.1074/jbc.272.51.32656.
101. Morales A., Lee H., Goñi F.M., Kolesnick R., Fernandez-Checa J.C. Sphingolipids and cell death. Apoptosis 2007, 12:923-939. http://www.ncbi.nlm.nih.gov/pubmed/17294080, 10.1007/s10495-007-0721-0.
102. Hannun Y.A., Obeid L.M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 2008, 9:139-150. http://www.ncbi.nlm.nih.gov/pubmed/18216770, 10.1038/nrm2329.
103. Hla T., Dannenberg A.J. Sphingolipid signaling in metabolic disorders. Cell Metab. 2012, 16:420-434. http://www.ncbi.nlm.nih.gov/pubmed/22982021, 10.1016/j.cmet.2012.06.017.
104. García-Ruiz C., Colell A., Marrí M., Moralles A., Calvo M., Enrich C., Fernández-Checa J.C. Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice. J. Clin. Investig. 2003, 111:197-208. http://www.ncbi.nlm.nih.gov/pubmed/12531875, 10.1172/JCI16010.
105. Marí M., Colell A., Morales A., Pañeda C., Varela-Nieto I., García-Ruiz C., et al. Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. J. Clin. Investig. 2004, 113:895-904. http://www.ncbi.nlm.nih.gov/pubmed/15067322, 10.1172/JCI19852.
106. Lin T., Genestier L., Pinkoski M.J., Castro A., Nicholas S., Mogil R., et al. Role of acidic sphingomyelinase in Fas/CD95-mediated cell death. J. Biol. Chem. 2000, 275:8657-8663. http://www.ncbi.nlm.nih.gov/pubmed/10722706, 10.1074/jbc.275.12.8657.
107. Moles A., Fernández-Checa J.C., Marí M., Marrí M. Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential. Hepatology 2009, 49:1297-1307. http://www.ncbi.nlm.nih.gov/pubmed/19116891, 10.1002/hep.22753.
108. Moles A., Tarrats N., Morales A., Domínguez M., Bataller R., Caballería J., García-Ruiz C. Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis. Am. J. Pathol. 2010, 177:1214-1224. http://www.ncbi.nlm.nih.gov/pubmed/20651240, 10.2353/ajpath.2010.091257.
109. Rabinowich L., Fishman S., Hubel E., Thurm T., Park W.J., Pewzner-Jung Y., Saroha A., Erez N., Halpern Z., Futerman A.H., Zvibel I. Sortilin deficiency improves the metabolic phenotype and reduces hepatic steatosis of mice subjected to diet-induced obesity. J. Hepatol. 2014, http://www.ncbi.nlm.nih.gov/pubmed/25173968, 10.1016/j.jhep.2014.08.030.
110. Liangpunsakul S., Rahmini Y., Ross R.A., Zhao Z., Xu Y., Crabb D.W. Imipramine blocks ethanol-induced ASMase activation, ceramide generation, and PP2A activation, and ameliorates hepatic steatosis in ethanol-fed mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302:G515-G523. http://www.ncbi.nlm.nih.gov/pubmed/22194417, 10.1152/ajpgi.00455.2011.
111. Boini K.M., Xia M., Abais J.M., Xu M., Li C.X., Li P.L. Acid sphingomyelinase gene knockout ameliorates hyperhomocysteinemic glomerular injury in mice lacking cystathionine-beta-synthase. PLoS One 2012, 7:e45020. http://www.ncbi.nlm.nih.gov/pubmed/23024785, 10.1371/journal.pone.0045020.
112. Henkel A.S., Dewey A.M., Anderson K.A., Olivares S., Green R.M. Reducing endoplasmic reticulum stress does not improve steatohepatitis in mice fed a methionine- and choline-deficient diet. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303:G54-G59. http://www.ncbi.nlm.nih.gov/pubmed/22556147, 10.1152/ajpgi.00052.2012.
113. Pinton P., Ferrari D., Rapizzi E., Di Virgilio F., Pozzan T., Rizzuto R. The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: Significance for the molecular mechanism of Bcl-2 action. EMBO J. 2001, 20:2690-2701. http://www.ncbi.nlm.nih.gov/pubmed/11387204, 10.1093/emboj/20.11.2690.
114. Fu S., Yang L., Li P., Hofmann O., Dicker L., Hide W., et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 2011, 473:528-531. http://www.ncbi.nlm.nih.gov/pubmed/21532591, 10.1038/nature09968.
115. Fu S., Watkins S.M., Hotamisligil G.S. The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metab. 2012, 15:623-634. http://www.ncbi.nlm.nih.gov/pubmed/22560215, 10.1016/j.cmet.2012.03.007.
116. Fucho R., Martínez L., Baulies A., Torres S., Tarrats N., Fernandez A., et al. ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis. J. Hepatol. 2014, http://www.ncbi.nlm.nih.gov/pubmed/24946279, 10.1016/j.jhep.2014.06.009.