Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function

Gonzalez-Rellan, María J.; Parracho, Tamara; Heras, Violeta; Rodrı́guez, Amaia; Fondevila, Marcos F.; Novoa, Eva María; Lima, Natalia; Varela‐Rey, Marta; Senra, Ana; Chantada-Vazquez, Maria; Ameneiro, Cristina; Bernardo, Giuseppe De; Fernández‐Ramos, David; Lopitz‐Otsoa, Fernando; Bilbao, Jon; Guallar, Diana; Fidalgo, Miguel; Bravo, Susana B.; Diéguez, Carlos; Martínez‐Chantar, María Luz; Millet, Óscar; Mato, José M.; Schwaninger, Markus; Prévot, Vincent; Crespo, Javier; Frühbeck, Gema; Iruzubieta, Paula; Nogueiras, Rubén

doi:10.1016/j.molmet.2023.101776

Cited by 6 publications

(2 citation statements)

References 40 publications

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“…Sustained O-GlcNAc elevation increases OGA expression and reduces cellular respiration and ROS generation [5]. Other research studies have shown that deregulated hyper-O-GlcNAcylation promotes the progression of NAFLD by reducing mitochondrial oxidation and promoting hepatic lipid accumulation [95]. Additionally, increased O-GlcNAcylation could resist oxidative stress and promote mitochondrial respiration in the retina of aged rats [96].…”

Section: Mitochondrial Oxidative Stressmentioning

confidence: 99%

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases

Qiu,

Cui,

Huang

et al. 2024

Antioxidants

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Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs.

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Section: Mitochondrial Oxidative Stressmentioning

confidence: 99%

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases

Qiu,

Cui,

Huang

et al. 2024

Antioxidants

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show abstract

“…In addition, deregulated hyper-O-GlcNAcylation favors NAFLD progression by reducing mitochondrial oxidation and promoting hepatic lipid accumulation. Hepatocyte-specific OGT downregulation can ameliorate NASH by improving mitochondrial functions [106]. Due to lipotoxicity, fat deposited in hepatocytes may induce inflammation via various pathways, causing the progression of NAFLD to NASH and increasing the risk of patients developing cirrhosis and even HCC [107].…”

Section: O-glcnacylation Contributes To the Progression Of Nafldmentioning

confidence: 99%

Biological Functions and Potential Therapeutic Significance of O-GlcNAcylation in Hepatic Cellular Stress and Liver Diseases

Mao,

Mu,

Gao

et al. 2024

Cells

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O-linked-β-D-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), which is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a post-translational modification involved in multiple cellular processes. O-GlcNAcylation of proteins can regulate their biological functions via crosstalk with other post-translational modifications, such as phosphorylation, ubiquitination, acetylation, and methylation. Liver diseases are a major cause of death worldwide; yet, key pathological features of the disease, such as inflammation, fibrosis, steatosis, and tumorigenesis, are not fully understood. The dysregulation of O-GlcNAcylation has been shown to be involved in some severe hepatic cellular stress, viral hepatitis, liver fibrosis, nonalcoholic fatty acid liver disease (NAFLD), malignant progression, and drug resistance of hepatocellular carcinoma (HCC) through multiple molecular signaling pathways. Here, we summarize the emerging link between O-GlcNAcylation and hepatic pathological processes and provide information about the development of therapeutic strategies for liver diseases.

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Metabolic effects of phospholipids extracted from capelin (Mallotus villosus) roe on HepG2 cells

Yin,

Luo,

Matsuoka

et al. 2024

Food Bioscience

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Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function

Cited by 6 publications

References 40 publications

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases

Biological Functions and Potential Therapeutic Significance of O-GlcNAcylation in Hepatic Cellular Stress and Liver Diseases

Metabolic effects of phospholipids extracted from capelin (Mallotus villosus) roe on HepG2 cells

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