The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production

Simões, Inês C. M.; Amorim, Ricardo; Teixeira, José; Karkucinska-Wieckowska, Agnieszka; Carvalho, Adriana; Pereira, Susana P.; Simões, Rui F.; Szymanska, Sylwia; Dąbrowski, Michał; Janikiewicz, Justyna; Dobrzyń, Agnieszka; Oliveira, Paulo J.; Potes, Yaiza; Wieckowski, Mariusz R.

doi:10.3390/ijms22136848

Open AccessArticle

The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production

by

Inês C. M. Simões

¹

,

Ricardo Amorim

^2,3,

José Teixeira

²,

Agnieszka Karkucinska-Wieckowska

⁴

,

Adriana Carvalho

²,

Susana P. Pereira

^2,5

,

Rui F. Simões

²,

Sylwia Szymanska

⁴

,

Michał Dąbrowski

¹

,

Justyna Janikiewicz

¹,

Agnieszka Dobrzyń

¹,

Paulo J. Oliveira

²,

Yaiza Potes

^1,*,† and

Mariusz R. Wieckowski

^1,*,†

¹

Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland

²

CNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal

³

CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal

⁴

Department of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland

⁵

Laboratory of Metabolism and Exercise (LametEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal

^*

Authors to whom correspondence should be addressed.

^†

These authors share senior authorship.

Int. J. Mol. Sci. 2021, 22(13), 6848; https://doi.org/10.3390/ijms22136848

Submission received: 20 May 2021 / Revised: 14 June 2021 / Accepted: 22 June 2021 / Published: 25 June 2021

(This article belongs to the Special Issue Targeting Mitochondria in Metabolic Diseases)

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Abstract

The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed with a high-fat plus high-sucrose diet for 16, 20, 22, and 24 weeks to induce NAFL. Up to the 20th week, an early mitochondrial remodeling with increased OXPHOS subunits levels and higher mitochondrial respiration occurred. Interestingly, a progressive loss of mitochondrial respiration along “Western diet” feeding was identified, accompanied by higher susceptibility to mitochondrial permeability transition pore opening. Importantly, our findings prove that mitochondrial alterations and subsequent impairment are independent of an excessive mitochondrial reactive oxygen species (ROS) generation, which was found to be progressively diminished along with disease progression. Instead, increased peroxisomal abundance and peroxisomal fatty acid oxidation-related pathway suggest that peroxisomes may contribute to hepatic ROS generation and oxidative damage, which may accelerate hepatic injury and disease progression. We show here for the first time the sequential events of mitochondrial alterations involved in non-alcoholic fatty liver disease (NAFLD) progression and demonstrate that mitochondrial ROS are not one of the first hits that cause NAFLD progression.

Keywords: non-alcoholic fatty liver; hepatic disease progression; metabolism; oxidative stress; liver autophagy

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MDPI and ACS Style

Simões, I.C.M.; Amorim, R.; Teixeira, J.; Karkucinska-Wieckowska, A.; Carvalho, A.; Pereira, S.P.; Simões, R.F.; Szymanska, S.; Dąbrowski, M.; Janikiewicz, J.; et al. The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production. Int. J. Mol. Sci. 2021, 22, 6848. https://doi.org/10.3390/ijms22136848

AMA Style

Simões ICM, Amorim R, Teixeira J, Karkucinska-Wieckowska A, Carvalho A, Pereira SP, Simões RF, Szymanska S, Dąbrowski M, Janikiewicz J, et al. The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production. International Journal of Molecular Sciences. 2021; 22(13):6848. https://doi.org/10.3390/ijms22136848

Chicago/Turabian Style

Simões, Inês C. M., Ricardo Amorim, José Teixeira, Agnieszka Karkucinska-Wieckowska, Adriana Carvalho, Susana P. Pereira, Rui F. Simões, Sylwia Szymanska, Michał Dąbrowski, Justyna Janikiewicz, and et al. 2021. "The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production" International Journal of Molecular Sciences 22, no. 13: 6848. https://doi.org/10.3390/ijms22136848

APA Style

Simões, I. C. M., Amorim, R., Teixeira, J., Karkucinska-Wieckowska, A., Carvalho, A., Pereira, S. P., Simões, R. F., Szymanska, S., Dąbrowski, M., Janikiewicz, J., Dobrzyń, A., Oliveira, P. J., Potes, Y., & Wieckowski, M. R. (2021). The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production. International Journal of Molecular Sciences, 22(13), 6848. https://doi.org/10.3390/ijms22136848

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The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production

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