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

Shu X, Liu J, Xu B, Wang H, Liu L, Zheng X, Chen J

Animals : an open access journal from MDPI29 Jul 2025Cited by 1 (Europe PMC)

PMID40805020PMCIDPMC12345487DOI10.3390/ani15152230PepBankPUB-40805020

Summary

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 MOTS-c 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 MOTS-c across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart MOTS-c 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

2 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In primary hepatocytes, 24 hours of MOTS‑c treatment significantly enriched ribosome, oxidative phosphorylation, PI3K-AKT and JAK-STAT pathways.
In plain wordsIn cells, MOTS‑c treatment changed activity of pathways linked to protein making, energy use and cell signalling.
Peptide
MOTS-c
Outcome
Not applicablePathway enrichment in primary hepatocytes after MOTS-c treatment
Study
n: not reported in source
primary hepatocytes
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
Dose not stated · 24 hoursAs given in this study.
Source sentences
Summary
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.
Show in the study text Report a problemFND-4080502006
02LabIn vitro (cells)Mechanism
In primary hepatocytes, Western blot confirmed that MOTS‑c activated the AKT signalling pathway.
In plain wordsIn cells, MOTS‑c switched on the AKT signalling pathway.
Peptide
MOTS-c
Outcome
IncreaseAKT signalling activation by MOTS-c
Study
n: not reported in source
primary hepatocytes
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-4080502007

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

03AnimalEndogenous levelAnimal study (in vivo)Other
In chickens, MOTS‑c was expressed in many tissues, with the highest expression in the heart.
In plain wordsIn chickens, the body's own MOTS‑c gene was active in many tissues, most strongly in the heart.
Peptide
MOTS-c
Outcome
Not applicableTissue distribution of chicken MOTS-c expression
Study
chickenn: not reported in source
Outcome group
Mitochondrial function · Whole body
Source sentences
Summary
Tissue expression profiling demonstrated widespread distribution of chicken MOTS-c across multiple tissues, with the highest expression levels in the heart.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4080502004
04AnimalEndogenous levelAnimal study (in vivo)Other
In chickens, fasting significantly reduced heart MOTS‑c expression.
In plain wordsIn chickens, fasting lowered the activity of the body's own MOTS‑c gene in the heart.
Peptide
MOTS-c
Outcome
DecreaseHeart MOTS-c expression after fasting
Study
chickenn: not reported in source
Comparator
Fed
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Fasting significantly reduced heart MOTS-c expression, suggesting potential metabolic regulatory functions.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4080502005

Studies that did not test the peptide alone3

In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking MOTS-c.

05Computer modelNot a test of MOTS-c aloneIn silicoOther
Alignment showed high sequence similarity in MOTS‑c coding regions between avian and mammalian species.
In plain wordsIn computer analysis, the MOTS‑c gene sequence of birds was very similar to that of mammals.
Peptide
MOTS-c
Outcome
Not applicableMOTS-c coding sequence similarity, avian versus mammalian
Study
n: not reported in source
bioinformatics sequence alignment
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
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 MOTS-c coding regions between avian and mammalian species.
In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.
Show in the study text Report a problemFND-4080502001
06Computer modelNot a test of MOTS-c aloneIn silicoOther
A single nucleotide deletion in avian MOTS‑c sequences led to divergent downstream amino acid sequences compared with mammalian homologs.
In plain wordsIn computer analysis, birds had a one-letter gene deletion that changes part of the MOTS‑c sequence compared with mammals.
Peptide
MOTS-c
Outcome
Not applicableSingle nucleotide deletion in avian MOTS-c sequence
Study
n: not reported in source
bioinformatics sequence alignment
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
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.
In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.
Show in the study text Report a problemFND-4080502002
07Computer modelNot a test of MOTS-c aloneIn silicoOther
Phylogenetic analysis of mRNA grouped pigeons with mammals, while protein sequences placed poultry and mammals on separate branches.
In plain wordsIn computer analysis, bird and mammal MOTS‑c protein sequences formed separate branches.
Peptide
MOTS-c
Outcome
Not applicablePhylogenetic grouping of MOTS-c sequences
Study
n: not reported in source
bioinformatics phylogenetic analysis
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
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.
In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.
Show in the study text Report a problemFND-4080502003

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Keywords

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