Abstract
Heart failure, a major cause of mortality, is increasingly viewed as a metabolic disorder involving mitochondrial dysfunction. Ketone body treatments have shown promise in enhancing mitochondrial function and improving heart failure outcomes. Long noncoding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not code for proteins, play critical roles in regulating gene expression and mitochondrial activity. Despite the known modulation of lncRNAs during heart failure, their specific functions under ketotic conditions remain poorly understood. Based on our preliminary findings, this study aims to explore the impact of ketosis on long noncoding RNAs (lncRNAs), particularly MALAT1, and their influence on mitochondrial function in AC16 human ventricular cardiomyocytes. AC16 cardiomyocytes were treated with β-hydroxybutyrate (0.5 mM, 1 mM, 5 mM) for 24, 48, and 72 hours to simulate ketosis. Gene expression of MALAT1, ketone oxidation enzymes (MCT1, BDH1, SCOT), mitochondrial biogenesis markers (PGC1α, TFAM), and antioxidant genes (NRF2, SOD1, SOD2) was quantified via qPCR. LncRRIsearch was employed to predict MALAT1’s interactions with mitochondrial-related mRNAs. Ketosis led to a significant increase in the expression of MALAT1, ketone oxidation enzymes, mitochondrial biogenesis markers, and antioxidant genes, with the most pronounced effects observed at 72 hours. Computational predictions revealed strong potential interactions between MALAT1 and the mRNAs of NRF2 and PGC1α. This study underscores the role of MALAT1 in regulating mitochondrial function during ketosis, suggesting its potential as a therapeutic target for heart failure interventions that involve lncRNAs.
Faculty Sponsors
Dr. Narasimman Gurusamy
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-2-2025 12:45 PM
End Date
4-3-2025 12:00 AM
Long Noncoding RNA MALAT1 in Mitochondrial Modulation Induced by Ketosis in Human Cardiomyocytes
Alvin Sherman Library
Heart failure, a major cause of mortality, is increasingly viewed as a metabolic disorder involving mitochondrial dysfunction. Ketone body treatments have shown promise in enhancing mitochondrial function and improving heart failure outcomes. Long noncoding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not code for proteins, play critical roles in regulating gene expression and mitochondrial activity. Despite the known modulation of lncRNAs during heart failure, their specific functions under ketotic conditions remain poorly understood. Based on our preliminary findings, this study aims to explore the impact of ketosis on long noncoding RNAs (lncRNAs), particularly MALAT1, and their influence on mitochondrial function in AC16 human ventricular cardiomyocytes. AC16 cardiomyocytes were treated with β-hydroxybutyrate (0.5 mM, 1 mM, 5 mM) for 24, 48, and 72 hours to simulate ketosis. Gene expression of MALAT1, ketone oxidation enzymes (MCT1, BDH1, SCOT), mitochondrial biogenesis markers (PGC1α, TFAM), and antioxidant genes (NRF2, SOD1, SOD2) was quantified via qPCR. LncRRIsearch was employed to predict MALAT1’s interactions with mitochondrial-related mRNAs. Ketosis led to a significant increase in the expression of MALAT1, ketone oxidation enzymes, mitochondrial biogenesis markers, and antioxidant genes, with the most pronounced effects observed at 72 hours. Computational predictions revealed strong potential interactions between MALAT1 and the mRNAs of NRF2 and PGC1α. This study underscores the role of MALAT1 in regulating mitochondrial function during ketosis, suggesting its potential as a therapeutic target for heart failure interventions that involve lncRNAs.
