Study summary · research use only
Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study combined human, mouse, and cell-based experiments on the mitochondrial-derived peptide MOTS-c in hepatitis B virus (HBV) infection. MOTS-c was measured by ELISA in 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, and its diagnostic value assessed by ROC analysis. Therapeutic effects were examined in HBV-infected mice and cells using transcriptomic sequencing, flow cytometry, immunofluorescence, electron microscopy, immunoprecipitation, and proteomics to explore MOTS-c interaction with myosin-9 (MYH9) and actin. MOTS-c levels negatively correlated with HBV DNA, distinguished chronic hepatitis B from healthy controls with an AUC of 0.9530, and were associated with reduced HBV replication (a 50-70% inhibition rate) and improved liver function without notable toxicity. MOTS-c was also linked to increased mitochondrial biogenesis via MYH9-actin pathways.
Abstract
Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism. In total, 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, were recruited for this study. MOTS-c levels were measured by ELISA and its diagnostic value was evaluated by receiving operating characteristic curve analysis. The therapeutic effect of MOTS-c was observed in multiple HBV-infected mice and cells through various techniques, including transcriptomic sequencing, flow cytometry, immunofluorescence and electron microscopy. Additionally, MOTS-c's potential interaction with myosin-9 (MYH9) and actin was predicted using immunoprecipitation, proteomics and target prediction software. MOTS-c negatively correlates with HBV DNA expression (R=-0.71), and its AUC (the area under the curve) for distinguishing CHB from healthy controls is 0.9530, and IA (immune reactive) from IC (inactive HBV carrier) is 0.8689. Inhibition of HBV replication (with a 50-70% inhibition rate) was observed alongside improved liver function without notable toxicity in vitro or in vivo. MOTS-c was found to promote mitochondrial biogenesis and enhance the MAVS (mitochondrial antiviral signalling protein) signalling pathway. The impact is dependent on MOTS-c's ability to regulate MYH9-actin-mediated mitochondrial homeostasis. MOTS-c has the potential to serve as a biomarker for the progression of HBV infection while also enhancing antiviral efficacy. These findings present a promising innovative approach for effectively treating patients with CHB. Furthermore, our research uncovers a novel role for MOTS-c in regulating MYH9-actin-mediated mitochondrial dynamics and contributing to mitochondrial biogenesis.
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