The DOI matches its Crossref record; 346 of the 348 references it cites were found in a registry or an index.
Mitochondrial dysfunction in NASH: Causes, consequences and possible means to prevent it
Abstract
Calorie-enriched diet and lack of exercise are causing a worldwide surge of obesity, insulin resistance and lipid accretion in liver (i.e. hepatic steatosis), which can lead to steatohepatitis. Steatosis and nonalcoholic steatohepatitis (NASH) can also be induced by drugs such as amiodarone, tamoxifen and some antiretroviral drugs, including stavudine and zidovudine. There is accumulating evidence that mitochondrial dysfunction (more particularly respiratory chain deficiency) plays a key role in the physiopathology of NASH whatever its initial cause. In contrast, the mitochondrial beta-oxidation of fatty acids can be either increased (as in insulin resistance-associated NASH) or decreased (as in drug-induced NASH). However, in both circumstances, generation of reactive oxygen species (ROS) by the damaged respiratory chain can be augmented. ROS generation in an environment enriched in lipids in turn induces lipid peroxidation which releases highly reactive aldehydic derivatives (e.g. malondialdehyde) that have diverse detrimental effects on hepatocytes and other hepatic cells. In hepatocytes, ROS, reactive nitrogen species and lipid peroxidation products further impair the respiratory chain, either directly or indirectly through oxidative damage to the mitochondrial genome. This consequently leads to the generation of more ROS and a vicious cycle occurs. Mitochondrial dysfunction can also lead to apoptosis or necrosis depending on the energy status of the cell. ROS and lipid peroxidation products also increase the generation of several cytokines (TNF-alpha, TGF-beta, Fas ligand) playing a key role in cell death, inflammation and fibrosis. Recent investigations have shown that some genetic polymorphisms can significantly increase the risk of steatohepatitis and that several drugs can prevent or even reverse NASH. Interestingly, most of these drugs could exert their beneficial effects by improving directly or indirectly mitochondrial function in liver. Finding a drug, which could fully prevent oxidative stress and mitochondrial dysfunction in NASH is a major challenge for the next decade.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“An increase in expression of Cytochrome C implies activation of its function as a single electron carrier in the electron transport chain catalyzing the reduction of oxygen molecule to water, thus leading to more ATP [34].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [34]
In the citing paper
“In patients with NASH, an increase in the ROS is associated with impaired mitochondrial electron transport chain (ETC) and loss in the ΔΨm [34].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [34]
In the citing paper
“Also, increase in the ROS is shown to damage mitochondrial DNA [43].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [43]
In the citing paper
“Indeed, mitochondrial DNA is extremely sensitive to oxidative/nitrative damage due to (A) its location closer to the inner mitochondrial membrane; (B) the relatively low amount of histone, anti-oxidant enzymes, and mtGSH, and (C) the low levels of polyamines and DNA repair enzymes [78], [79].”
Citations
Cites
1 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
RetractedThe metabolic syndrome—a new worldwide definition
Alberti, K. G. M., Zimmet, P., & Shaw, J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67402-8 · Cited by 9,352
Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,317
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,755
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Nonalcoholic Fatty Liver Disease
Angulo, P. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011775 · Cited by 5,228
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
Flagged first, then by citations
2 of the 348 references couldn’t be matched to a known paper.
Research works printed but not linked: 6
- Abbey-Toby, 2005, β-Aminoisobutyric acid alleviates steatohepatitis in a murine model of diabetes and obesity, Virchows Arch., 447, 305
- Begriche, 2005, A thymine catabolite, β-aminoisobutyric acid, reduces hepatic dysfunction and metabolic disorders in overweight or obese mice, J. Hepatol., 42, 243
- Fiorini, 2002, Primary non-function in steatotic livers is due to differential Toll-like expression and endotoxin sensitivity, Hepatology, 36, 198
- Haque, 2002, Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte mitochondrial DNA depletion, Hepatology, 36, 403
- Igoudjil, 2005, Mitochondrial and metabolic disturbances induced by high dose of stavudine in mice are alleviated by coadministration of l-carnitine. Possible role of PPAR-α, J. Hepatol., 42, 247
- Sutton, 2003, The Ala-9Val dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria, Pharmacogentics, 13, 145, 10.1097/00008571-200303000-00004 · DOI
Cited by
Sorted by citations
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.12.012 · Cited by 3,119
Mitochondrial dysfunction: mechanisms and advances in therapy
Yao, Z., Li, H., Liao, P., Chen, L., Pan, Y., Zheng, Y., Zhang, C., Liu, D., Zheng, M., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01839-8 · Cited by 1,382
Decoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Rolo, A. P., Teodoro, J. S., & Palmeira, C. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.003 · Cited by 955
Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease
Lebeaupin, C., Vallée, D., Hazari, Y., Hetz, C. A., Chevet, É., & Bailly‐Maitre, B. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.06.008 · Cited by 971
Metadata
- Authors
- Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B.
- Affiliations
- Inserm (FR)
- Corresponding author
- Fromenty, Bernard
- Venue
- Mitochondrion
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 6
- Issue
- 1
- Pages
- 1-28
- ISSN
- 1567-7249 (ISSN-L)
- OpenAlex
- W1978045299
- Cited by
- 753
- References
- 348
- Citations by year
- 2026: 24 · 2025: 28 · 2024: 33 · 2023: 27 · 2022: 55 · 2021: 47 · 2020: 43 · 2019: 48 · 2018: 43 · 2017: 32 · 2016: 39 · 2015: 39 · 2014: 38 · 2013: 39 · 2012: 35
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mitochondrion (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- mitochondrial dysfunction, nonalcoholic steatohepatitis, hepatic steatosis, respiratory chain deficiency, reactive oxygen species, lipid peroxidation, malondialdehyde, mitochondrial DNA damage, insulin resistance, drug-induced liver injury, fatty acid beta-oxidation, apoptosis, cytokines, liver fibrosis, genetic polymorphism, oxidative stress
- MeSH terms
- Animals, Drug Therapy, Fatty Liver, Hepatitis, Humans, Mitochondria, Liver, Mitochondrial Diseases, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
