{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:45:46Z","timestamp":1793339146117,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK56345 and R01DK67763"],"award-info":[{"award-number":["R01DK56345 and R01DK67763"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The liver is one of the richest organs in mitochondria, serving as a hub for key metabolic pathways such as \u03b2-oxidation, the tricarboxylic acid (TCA) cycle, ketogenesis, respiratory activity, and adenosine triphosphate (ATP) synthesis, all of which provide metabolic energy for the entire body. Mitochondrial dysfunction has been linked to subcellular organelle dysfunction in liver diseases, particularly fatty liver disease. Acute fatty liver of pregnancy (AFLP) is a life-threatening liver disorder unique to pregnancy, which can result in serious maternal and fetal complications, including death. Pregnant mothers with this disease require early detection, prompt delivery, and supportive maternal care. AFLP was considered a mysterious illness and though its pathogenesis has not been fully elucidated, molecular research over the past two decades has linked AFLP to mitochondrial dysfunction and defects in fetal fatty-acid oxidation (FAO). Due to deficient placental and fetal FAO, harmful 3-hydroxy fatty acid metabolites accumulate in the maternal circulation, causing oxidative stress and microvesicular fatty infiltration of the liver, resulting in AFLP. In this review, we provide an overview of AFLP and mitochondrial FAO followed by discussion of how altered mitochondrial function plays an important role in the pathogenesis of AFLP.<\/jats:p>","DOI":"10.3390\/ijms23073595","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T15:31:21Z","timestamp":1648222281000},"page":"3595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-7359","authenticated-orcid":false,"given":"Raghu","family":"Ramanathan","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65211, USA"},{"name":"Harry S. Truman Memorial Veterans Medical Center, University of Missouri, Columbia, MO 65201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5646-9014","authenticated-orcid":false,"given":"Jamal A.","family":"Ibdah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65211, USA"},{"name":"Harry S. Truman Memorial Veterans Medical Center, University of Missouri, Columbia, MO 65201, USA"},{"name":"Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.yexcr.2011.07.009","article-title":"Hepatic response to aluminum toxicity: Dyslipidemia and liver diseases","volume":"317","author":"Mailloux","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_2","first-page":"387626","article-title":"Mitochondrial roles and cytoprotection in chronic liver injury","volume":"2012","author":"Hamelin","year":"2012","journal-title":"Biochem. Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E484","DOI":"10.1152\/ajpendo.00492.2015","article-title":"Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity","volume":"310","author":"Patterson","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1194\/jlr.M023382","article-title":"Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver","volume":"53","author":"Satapati","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1365-2362.2008.01963.x","article-title":"Severe liver steatosis correlates with nitrosative and oxidative stress in rats","volume":"38","author":"Grattagliano","year":"2008","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4137\/JCD.S39824","article-title":"Mechanism of Hepatocyte Apoptosis","volume":"9","author":"Cao","year":"2016","journal-title":"J. Cell Death"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"456.e1","DOI":"10.1016\/j.ajog.2013.07.006","article-title":"Acute fatty liver of pregnancy: Clinical outcomes and expected duration of recovery","volume":"209","author":"Nelson","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.11622\/smedj.2018001","article-title":"Outcomes and risk factors of patients with acute fatty liver of pregnancy: A multicentre retrospective study","volume":"59","author":"Gao","year":"2018","journal-title":"Singap. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7397","DOI":"10.3748\/wjg.v12.i46.7397","article-title":"Acute fatty liver of pregnancy: An update on pathogenesis and clinical implications","volume":"12","author":"Ibdah","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00404-006-0203-6","article-title":"Acute fatty liver of pregnancy","volume":"274","author":"Mjahed","year":"2006","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/hep.1840050615","article-title":"Acute fatty liver of pregnancy: A clinicopathologic study of 35 cases","volume":"5","author":"Rolfes","year":"1985","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1155\/2006\/638131","article-title":"Acute fatty liver of pregnancy","volume":"20","author":"Ko","year":"2006","journal-title":"Can. J. Gastroenterol."},{"key":"ref_14","first-page":"55","article-title":"Mitochondrial fatty acid oxidation and acute fatty liver of pregnancy","volume":"13","author":"Treem","year":"2002","journal-title":"Semin. Gastrointest. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/290457a0","article-title":"Sequence and organization of the human mitochondrial genome","volume":"290","author":"Anderson","year":"1981","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10456-018-9611-z","article-title":"BI1 is associated with microvascular protection in cardiac ischemia reperfusion injury via repressing Syk-Nox2-Drp1-mitochondrial fission pathways","volume":"21","author":"Zhou","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.redox.2017.11.004","article-title":"DUSP1 alleviates cardiac ischemia\/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways","volume":"14","author":"Jin","year":"2018","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108241","DOI":"10.1016\/j.abb.2019.108241","article-title":"The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes","volume":"680","author":"Sumneang","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12447","DOI":"10.1111\/jpi.12447","article-title":"Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin","volume":"64","author":"Ding","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104553","DOI":"10.1016\/j.phrs.2019.104553","article-title":"Dynamin-related protein 1: A protein critical for mitochondrial fission, mitophagy, and neuronal death in Parkinson\u2019s disease","volume":"151","author":"Feng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s10495-016-1295-5","article-title":"Mitochondrial dynamics during cell cycling","volume":"21","author":"Horbay","year":"2016","journal-title":"Apoptosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12883","article-title":"Mitochondrial dynamics regulating chemoresistance in gynecological cancers","volume":"1350","author":"Kong","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13428","DOI":"10.1111\/apha.13428","article-title":"Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1-dependent way","volume":"229","author":"Ding","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mito.2019.11.006","article-title":"OPA1 regulates respiratory supercomplexes assembly: The role of mitochondrial swelling","volume":"51","author":"Jang","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.tcb.2007.08.006","article-title":"Regulation of mitochondrial fusion and division","volume":"17","author":"Cerveny","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1080\/15384101.2015.1026517","article-title":"Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes","volume":"14","author":"Zhang","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/MOL.0b013e328328d0a4","article-title":"PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure","volume":"20","author":"Auwerx","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.fct.2017.08.020","article-title":"Induction of mitochondrial biogenesis protects against acetaminophen hepatotoxicity","volume":"108","author":"Du","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/03602532.2011.604086","article-title":"Central role of mitochondria in drug-induced liver injury","volume":"44","author":"Pessayre","year":"2012","journal-title":"Drug Metab. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1055\/s-0035-1562945","article-title":"Fatty Acid and Glucose Sensors in Hepatic Lipid Metabolism: Implications in NAFLD","volume":"35","author":"Vacca","year":"2015","journal-title":"Semin. Liver Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"637027","DOI":"10.1155\/2014\/637027","article-title":"Nonalcoholic Fatty liver disease: Pathogenesis and therapeutics from a mitochondria-centric perspective","volume":"2014","author":"Gusdon","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: Guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41467-017-00521-8","article-title":"GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1128\/MCB.00677-14","article-title":"Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance","volume":"34","author":"Meakin","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.phrs.2018.11.020","article-title":"Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies","volume":"139","author":"Skoda","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1002\/jcp.27597","article-title":"Mitochondrial quality control in cardiac cells: Mechanisms and role in cardiac cell injury and disease","volume":"234","author":"Tahrir","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Pawlowska, E., Szczepanska, J., and Kaarniranta, K. (2019). Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010210"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and selective fusion govern mitochondrial segregation and elimination by autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"C308","DOI":"10.1152\/ajpcell.00056.2010","article-title":"Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation","volume":"300","author":"Kim","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1111\/j.1440-1746.2006.04640.x","article-title":"Role of mitochondria in non-alcoholic fatty liver disease","volume":"22","author":"Pessayre","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/embo-reports\/kve071","article-title":"Mechanisms of nutritional and hormonal regulation of lipogenesis","volume":"2","author":"Kersten","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.mam.2004.06.004","article-title":"Carnitine palmitoyltransferases 1 and 2: Biochemical, molecular and medical aspects","volume":"25","author":"Bonnefont","year":"2004","journal-title":"Mol. Asp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3350\/cmh.2013.19.3.210","article-title":"Nonalcoholic fatty liver disease: Molecular mechanisms for the hepatic steatosis","volume":"19","author":"Koo","year":"2013","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3748\/wjg.14.193","article-title":"Nonalcoholic fatty liver disease and mitochondrial dysfunction","volume":"14","author":"Wei","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/hep.1840380426","article-title":"Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis","volume":"38","author":"Rubio","year":"2003","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1021\/acs.chemrev.7b00510","article-title":"Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism","volume":"118","author":"Walsh","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.sbi.2013.06.013","article-title":"Revealing various coupling of electron transfer and proton pumping in mitochondrial respiratory chain","volume":"23","author":"Sun","year":"2013","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S405","DOI":"10.2337\/diabetes.51.2007.S405","article-title":"Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: Role in beta-cell adaptation and failure in the etiology of diabetes","volume":"51","author":"Prentki","year":"2002","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cmet.2015.04.004","article-title":"Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis","volume":"21","author":"Koliaki","year":"2015","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1124\/jpet.106.114546","article-title":"Tamoxifen inhibits topoisomerases, depletes mitochondrial DNA, and triggers steatosis in mouse liver","volume":"321","author":"Larosche","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0030-1267539","article-title":"Novel insights into the pathophysiology of nonalcoholic fatty liver disease","volume":"30","author":"Feldstein","year":"2010","journal-title":"Semin. Liver Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.7150\/ijms.36516","article-title":"Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases","volume":"16","author":"Tabassum","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/10799893.2019.1676259","article-title":"Ripk3 mediates cardiomyocyte necrosis through targeting mitochondria and the JNK-Bnip3 pathway under hypoxia-reoxygenation injury","volume":"39","author":"Song","year":"2019","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101314","DOI":"10.1016\/j.redox.2019.101314","article-title":"Carbon monoxide releasing molecule-A1 improves nonalcoholic steatohepatitis via Nrf2 activation mediated improvement in oxidative stress and mitochondrial function","volume":"28","author":"Upadhyay","year":"2020","journal-title":"Redox Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Xu, J., Peng, Y., Zeng, Y., Hua, Y.Q., and Xu, X.L. (2019). 2, 3, 4\u2019, 5-tetrahydroxystilbene-2-0-\u03b2-d Glycoside Attenuates Age- and Diet-Associated Non-Alcoholic Steatohepatitis and Atherosclerosis in LDL Receptor Knockout Mice and Its Possible Mechanisms. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071617"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fcell.2019.00248","article-title":"Fatty Liver Due to Increased","volume":"7","author":"Knebel","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12452","DOI":"10.1111\/jpi.12452","article-title":"Melatonin and serotonin: Mediators in the symphony of plant morphogenesis","volume":"64","author":"Erland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101284","DOI":"10.1016\/j.redox.2019.101284","article-title":"Biochemical basis and metabolic interplay of redox regulation","volume":"26","author":"Zhang","year":"2019","journal-title":"Redox Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101167","DOI":"10.1016\/j.redox.2019.101167","article-title":"Peroxisomal regulation of redox homeostasis and adipocyte metabolism","volume":"24","author":"Liu","year":"2019","journal-title":"Redox Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/10799893.2018.1431278","article-title":"Leptin and chronic kidney diseases","volume":"38","author":"Mao","year":"2018","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1002\/1873-3468.13741","article-title":"Rotenone-induced reactive oxygen species signal the recruitment of STAT3 to mitochondria","volume":"594","author":"Mohammed","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.3389\/fphys.2019.01496","article-title":"Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms","volume":"10","author":"Delmar","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zeeshan, H.M., Lee, G.H., Kim, H.R., and Chae, H.J. (2016). Endoplasmic Reticulum Stress and Associated ROS. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030327"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/hep.29689","article-title":"New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases","volume":"67","author":"Win","year":"2018","journal-title":"Hepatology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0163-7258(95)00012-6","article-title":"Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity","volume":"67","author":"Fromenty","year":"1995","journal-title":"Pharmacol. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/01.RES.88.5.529","article-title":"Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction","volume":"88","author":"Ide","year":"2001","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1172\/JCI117158","article-title":"Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients","volume":"93","author":"Kamijo","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000134727","article-title":"Fluorescence in situ hybridization mapping of the alpha and beta subunits (HADHA and HADHB) of human mitochondrial fatty acid beta-oxidation multienzyme complex to 2p23 and their evolution","volume":"79","author":"Aoyama","year":"1997","journal-title":"Cytogenet. Genome Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8077","DOI":"10.1074\/jbc.274.12.8077","article-title":"Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region","volume":"274","author":"Orii","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJM199906033402204","article-title":"A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women","volume":"340","author":"Ibdah","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/00008480-199810060-00014","article-title":"Clinical and biochemical features of fatty acid oxidation disorders","volume":"10","author":"Rinaldo","year":"1998","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/0887-8994(96)00021-5","article-title":"The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency","volume":"14","author":"Pons","year":"1996","journal-title":"Pediatr. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1172\/JCI2091","article-title":"Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation","volume":"102","author":"Ibdah","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1073\/pnas.92.3.841","article-title":"The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy","volume":"92","author":"Sims","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0005-2760(94)90064-7","article-title":"Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein","volume":"1215","author":"IJlst","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/0016-5085(91)90228-D","article-title":"Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring","volume":"100","author":"Schoeman","year":"1991","journal-title":"Gastroenterology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0140-6736(93)92993-4","article-title":"Pregnancy and fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency","volume":"341","author":"Wilcken","year":"1993","journal-title":"Lancet"},{"key":"ref_80","first-page":"339","article-title":"Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency","volume":"19","author":"Treem","year":"1994","journal-title":"Hepatology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1067\/mob.2002.125893","article-title":"Fetal genotypes and pregnancy outcomes in 35 families with mitochondrial trifunctional protein mutations","volume":"187","author":"Yang","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1001\/jama.288.17.2163","article-title":"Prospective screening for pediatric mitochondrial trifunctional protein defects in pregnancies complicated by liver disease","volume":"288","author":"Yang","year":"2002","journal-title":"JAMA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ajg.2015.430","article-title":"ACG Clinical Guideline: Liver Disease and Pregnancy","volume":"111","author":"Tran","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/hep.31559","article-title":"Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases","volume":"73","author":"Sarkar","year":"2021","journal-title":"Hepatology"},{"key":"ref_85","first-page":"63","article-title":"Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein\/Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency","volume":"31","author":"Viau","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1067\/mpd.2001.111503","article-title":"Molecular prenatal diagnosis in families with fetal mitochondrial trifunctional protein mutations","volume":"138","author":"Ibdah","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1203\/00006450-200001000-00010","article-title":"Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy","volume":"47","author":"Innes","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/jog.12609","article-title":"Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency","volume":"41","author":"Kobayashi","year":"2015","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/mgme.2000.3135","article-title":"Placental floor infarction complicating the pregnancy of a fetus with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency","volume":"72","author":"Matern","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tiv.2016.06.007","article-title":"Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle","volume":"36","author":"Cecatto","year":"2016","journal-title":"Toxicol. In Vitro"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1460-9592.2010.03274.x","article-title":"Perioperative management of a child with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency","volume":"20","author":"Steinmann","year":"2010","journal-title":"Paediatr. Anaesth."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1023\/A:1025163204165","article-title":"High activity of fatty acid oxidation enzymes in human placenta: Implications for fetal-maternal disease","volume":"26","author":"Oey","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10545-006-0199-x","article-title":"Fatty acid oxidation in the human fetus: Implications for fetal and adult disease","volume":"29","author":"Oey","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3945\/jn.108.098608","article-title":"Long chain PUFA transport in human term placenta","volume":"139","author":"Cunningham","year":"2009","journal-title":"J. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1203\/01.PDR.0000161413.42874.74","article-title":"Long-chain fatty acid oxidation during early human development","volume":"57","author":"Oey","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"730569","DOI":"10.1155\/2013\/730569","article-title":"Retrospective study of seven cases with acute Fatty liver of pregnancy","volume":"2013","author":"Dwivedi","year":"2013","journal-title":"ISRN Obstet. Gynecol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.neuint.2010.03.025","article-title":"Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain","volume":"56","author":"Tonin","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_98","first-page":"221","article-title":"LCHAD (long-chain 3-hydroxyacyl-CoA dehydrogenase) deficiency as a cause of sudden death of a three months old infant","volume":"6","author":"Wierzba","year":"2002","journal-title":"Med. Wieku Rozw."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s10545-005-0533-8","article-title":"Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency","volume":"28","author":"Olpin","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/hep.23245","article-title":"Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress","volume":"51","author":"Natarajan","year":"2010","journal-title":"Hepatology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/j.1440-1746.2006.04231.x","article-title":"Oxidative stress in the development of liver cirrhosis: A comparison of two different experimental models","volume":"21","author":"Natarajan","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/j.1440-1746.2006.04313.x","article-title":"Oxidative stress in experimental liver microvesicular steatosis: Role of mitochondria and peroxisomes","volume":"21","author":"Natarajan","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1258\/om.2011.100071","article-title":"Acute fatty liver of pregnancy: An update on mechanisms","volume":"4","author":"Natarajan","year":"2011","journal-title":"Obstet. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1002\/hep.27175","article-title":"Saturated free fatty acids induce cholangiocyte lipoapoptosis","volume":"60","author":"Natarajan","year":"2014","journal-title":"Hepatology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.jhep.2010.01.003","article-title":"Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis","volume":"52","author":"Akazawa","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/hep.27341","article-title":"Cholangiocyte lipoapoptosis: Implications for biliary damage during nonalcoholic fatty liver disease","volume":"60","author":"Glaser","year":"2014","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1194\/jlr.M071357","article-title":"FoxO3 increases miR-34a to cause palmitate-induced cholangiocyte lipoapoptosis","volume":"58","author":"Natarajan","year":"2017","journal-title":"J. Lipid Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:43:31Z","timestamp":1760136211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":107,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073595"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073595","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,25]]}}}