Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator

MOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c codin...

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Main Authors: Xin Shu, Jiying Liu, Bingjie Xu, Hui Wang, Li Liu, Xiaotong Zheng, Jianfei Chen
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Animals
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Online Access:https://www.mdpi.com/2076-2615/15/15/2230
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author Xin Shu
Jiying Liu
Bingjie Xu
Hui Wang
Li Liu
Xiaotong Zheng
Jianfei Chen
author_facet Xin Shu
Jiying Liu
Bingjie Xu
Hui Wang
Li Liu
Xiaotong Zheng
Jianfei Chen
author_sort Xin Shu
collection DOAJ
description MOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c coding sequences across major poultry species through bioinformatics analysis and experimental validation. The alignment results showed high sequence similarity in the <i>MOTS-c</i> coding regions between avian and mammalian species. However, a single nucleotide deletion was identified in avian sequences at the position corresponding to the fourth amino acid residue of mammalian homologs, resulting in divergent downstream amino acid sequences. Despite this deletion, several residues were conserved across species. Phylogenetic analysis of mRNA sequences grouped pigeons with mammals, while protein sequence analysis revealed that poultry and mammals form separate branches, highlighting the divergence between avian and mammalian MOTS-c sequences. Tissue expression profiling demonstrated widespread distribution of chicken <i>MOTS-c</i> across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart <i>MOTS-c</i> expression, suggesting potential metabolic regulatory functions. Functional analysis of MOTS-c in primary hepatocytes revealed significant enrichment of the ribosome, oxidative phosphorylation, and key signaling pathways (PI3K-AKT and JAK-STAT) following 24 hours of treatment. Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway. This study represents the first comprehensive characterization of avian MOTS-c, providing critical insights into its evolutionary conservation and its potential functional roles in gene expression and cellular metabolism. Our findings establish a foundation for further investigation into the functions of mitochondrial-encoded peptides in avian species.
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spelling doaj-art-126f0d5e44ca478797bc25558de375d42025-08-20T04:00:50ZengMDPI AGAnimals2076-26152025-07-011515223010.3390/ani15152230Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic RegulatorXin Shu0Jiying Liu1Bingjie Xu2Hui Wang3Li Liu4Xiaotong Zheng5Jianfei Chen6Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaMOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c coding sequences across major poultry species through bioinformatics analysis and experimental validation. The alignment results showed high sequence similarity in the <i>MOTS-c</i> coding regions between avian and mammalian species. However, a single nucleotide deletion was identified in avian sequences at the position corresponding to the fourth amino acid residue of mammalian homologs, resulting in divergent downstream amino acid sequences. Despite this deletion, several residues were conserved across species. Phylogenetic analysis of mRNA sequences grouped pigeons with mammals, while protein sequence analysis revealed that poultry and mammals form separate branches, highlighting the divergence between avian and mammalian MOTS-c sequences. Tissue expression profiling demonstrated widespread distribution of chicken <i>MOTS-c</i> across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart <i>MOTS-c</i> expression, suggesting potential metabolic regulatory functions. Functional analysis of MOTS-c in primary hepatocytes revealed significant enrichment of the ribosome, oxidative phosphorylation, and key signaling pathways (PI3K-AKT and JAK-STAT) following 24 hours of treatment. Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway. This study represents the first comprehensive characterization of avian MOTS-c, providing critical insights into its evolutionary conservation and its potential functional roles in gene expression and cellular metabolism. Our findings establish a foundation for further investigation into the functions of mitochondrial-encoded peptides in avian species.https://www.mdpi.com/2076-2615/15/15/2230poultrymitochondrial-derived peptideMOTS-cRNA-seqAKT signaling pathway
spellingShingle Xin Shu
Jiying Liu
Bingjie Xu
Hui Wang
Li Liu
Xiaotong Zheng
Jianfei Chen
Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
Animals
poultry
mitochondrial-derived peptide
MOTS-c
RNA-seq
AKT signaling pathway
title Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
title_full Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
title_fullStr Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
title_full_unstemmed Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
title_short Characterization of the Avian Mitochondrial-Derived Peptide MOTS-c and Its Potential Role as a Metabolic Regulator
title_sort characterization of the avian mitochondrial derived peptide mots c and its potential role as a metabolic regulator
topic poultry
mitochondrial-derived peptide
MOTS-c
RNA-seq
AKT signaling pathway
url https://www.mdpi.com/2076-2615/15/15/2230
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