Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases

Madan Kumar Arumugam; Thiyagarajan Gopal; Rakhee Rathnam Kalari Kandy; Lokesh Kumar Boopathy; Sathish Kumar Perumal; Murali Ganesan; Karuna Rasineni; Terrence M Donohue Jr; Natalia A Osna; Kusum K Kharbanda

doi:10.3390/biology12101311

Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases

Biology (Basel). 2023 Oct 5;12(10):1311. doi: 10.3390/biology12101311.

Authors

Madan Kumar Arumugam^{1

2

3}, Thiyagarajan Gopal⁴, Rakhee Rathnam Kalari Kandy⁵, Lokesh Kumar Boopathy⁴, Sathish Kumar Perumal^{1

2}, Murali Ganesan^{1

2}, Karuna Rasineni⁶, Terrence M Donohue Jr^{1

2

6}, Natalia A Osna^{1

2}, Kusum K Kharbanda^{1

2

6}

Affiliations

¹ Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
² Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
³ Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.
⁴ Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.
⁵ Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD 21201, USA.
⁶ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Abstract

The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed "metabolic-dysfunction-associated steatotic liver disease" (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.

Keywords: alcohol-associated liver disease; hepatocytes; liver; metabolic-dysfunction-associated steatotic liver disease; mitochondria; steatotic liver diseases.

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