Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Mar 25;23(7):3595.
doi: 10.3390/ijms23073595.

Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy

Raghu Ramanathan  1   2 , Jamal A Ibdah  1   2   3
Affiliations
Review

Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy

Raghu Ramanathan et al. Int J Mol Sci. .

Abstract

The liver is one of the richest organs in mitochondria, serving as a hub for key metabolic pathways such as β-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.

Keywords: acute fatty liver of pregnancy; liver; long chain 3-hydroxyacyl Co-A; mitochondrial dysfunction; mitochondrial trifunctional protein; β-oxidation.

PubMed Disclaimer

Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A schematic representation of free fatty acid transport to mitochondria. TG: Triglyceride; FFA: Free fatty acid.
Figure 2
Figure 2
The role of mitochondria in fatty-acid oxidation and energy production. Excessive electron leakage causes excessive ROS generation and cellular injury. FFA: Free fatty acid; NADH: Nicotinamide adenine dinucleotide; FADH: Flavin adenine dinucleotide; ROS: Reactive oxygen species; ETC: Electron transport chain; MOM: Mitochondrial outer membrane; MIM: Mitochondrial inner membrane; ADP: Adenosine diphosphate; e: electrons; ATP: Adenosine triphosphate; TNF-α: Tumor necrosis factor-α; NF-KB: Nuclear factor-KB; IL: Interleukin; MAPKs: Mitogen activated protein kinases; JNK: c-jun N terminal kinase; AMPK: AMP-activated protein kinase.
Figure 3
Figure 3
A schematic representation of possible mechanisms leading to the development of maternal AFLP associated with fetal LCHAD deficiency. MTP: Mitochondrial Trifunctional Protein; LCHAD: Long chain acyl-CoA dehydrogenase.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mailloux R.J., Lemire J., Appanna V.D. Hepatic response to aluminum toxicity: Dyslipidemia and liver diseases. Exp. Cell Res. 2011;317:2231–2238. doi: 10.1016/j.yexcr.2011.07.009. - DOI - PubMed
    1. Degli Esposti D., Hamelin J., Bosselut N., Saffroy R., Sebagh M., Pommier A., Martel C., Lemoine A. Mitochondrial roles and cytoprotection in chronic liver injury. Biochem. Res. Int. 2012;2012:387626. doi: 10.1155/2012/387626. - DOI - PMC - PubMed
    1. Patterson R.E., Kalavalapalli S., Williams C.M., Nautiyal M., Mathew J.T., Martinez J., Reinhard M.K., McDougall D.J., Rocca J.R., Yost R.A., et al. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity. Am. J. Physiol. Endocrinol. Metab. 2016;310:E484–E494. doi: 10.1152/ajpendo.00492.2015. - DOI - PMC - PubMed
    1. Satapati S., Sunny N.E., Kucejova B., Fu X., He T.T., Méndez-Lucas A., Shelton J.M., Perales J.C., Browning J.D., Burgess S.C. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver. J. Lipid Res. 2012;53:1080–1092. doi: 10.1194/jlr.M023382. - DOI - PMC - PubMed
    1. Grattagliano I., Caraceni P., Calamita G., Ferri D., Gargano I., Palasciano G., Portincasa P. Severe liver steatosis correlates with nitrosative and oxidative stress in rats. Eur. J. Clin. Investig. 2008;38:523–530. doi: 10.1111/j.1365-2362.2008.01963.x. - DOI - PubMed

Supplementary concepts