An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model

Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine de...

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Published in:Scientific reports 2024-03, Vol.14 (1), p.6348-6348, Article 6348
Main Authors: García-Carrillo, Rosendo, Molina-Pelayo, Francisco A., Zarate-Lopez, David, Cabrera-Aguilar, Alejandro, Ortega-Domínguez, Bibiana, Domínguez-López, Mariana, Chiquete-Félix, Natalia, Dagnino-Acosta, Adan, Velasco-Loyden, Gabriela, Chávez, Enrique, Castro-Sánchez, Luis, de Sánchez, Victoria Chagoya
Format: Article
Language:English
Subjects:
631/67
631/80
Adenosine
ATP
Bioenergetics
Cardiolipin
Cirrhosis
Diethylnitrosamine
Electron transport chain
Hepatocellular carcinoma
Humanities and Social Sciences
Lecithin
Liver
Liver cancer
Mitochondria
Mitochondrial DNA
multidisciplinary
Parenchyma
Phosphatidylcholine
Science
Science (multidisciplinary)
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Summary:Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine derivative, IFC-305, which improves mitochondrial function, and it has been proposed as a therapeutic candidate for HCC. We aimed to determine the role of IFC-305 on both mitochondrial structure and bioenergetics in a sequential cirrhosis-HCC model in rats. Our results showed that IFC-305 administration decreased the number and size of liver tumors, reduced the expression of tumoral markers, and reestablished the typical architecture of the hepatic parenchyma. The livers of treated rats showed a reduction of mitochondria number, recovery of the mtDNA/nDNA ratio, and mitochondrial length. Also, IFC-305 increased cardiolipin and phosphatidylcholine levels and promoted hmwSC reorganization with changes in the expression levels of hmwSC assembly-related genes. IFC-305 in HCC modified the expression of several genes encoding elements of electron transport chain complexes and increased the ATP levels by recovering the complex I, III, and V activity. We propose that IFC-305 restores the mitochondrial bioenergetics in HCC by normalizing the quantity, morphology, and function of mitochondria, possibly as part of its hepatic restorative effect.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-56306-9