This research-grade peptide is supplied exclusively for laboratory and experimental use. MOTS-C is examined in experimental models investigating mitochondrial signaling, cellular energy regulation, and metabolic adaptation. Research interest centers on how cells respond to energetic stress and efficiency-related signals.
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino acid peptide encoded by the mitochondrial genome (mtDNA). Discovered in 2015, it functions as a mitochondrial-derived peptide (MDP) with systemic regulatory roles. Unlike traditional mitochondrial proteins, MOTS-c translocates from mitochondria to the nucleus, influencing gene expression and metabolic pathways. Its molecular-level mechanism of action (MoA) centers on modulating cellular energy homeostasis, primarily through AMPK activation and purine metabolism interference. Recent studies (2025-2026) highlight its potential in metabolic disorders, aging, and neurodegeneration, with applications as an exercise mimetic. Structurally distinct from other MDPs like Humanin (a 24-amino acid peptide), MOTS-c shares cytoprotective effects but targets different pathways, making it promising for neurodegenerative diseases such as Alzheimer's and Parkinson's.
Core Molecular Mechanism
At the molecular level, MOTS-c regulates metabolism by inhibiting the folate/methionine cycle in the nucleus. It binds to nuclear factors, reducing de novo purine biosynthesis, which leads to accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). AICAR is a potent activator of AMP-activated protein kinase (AMPK), mimicking energy stress and triggering catabolic pathways.
- Glycolysis Enhancement and AICAR Buildup: MOTS-c promotes glycolysis by shifting cellular reliance from oxidative phosphorylation (OXPHOS) to glycolytic flux under stress. This is achieved via AICAR-mediated AMPK activation, which phosphorylates targets like ACC (acetyl-CoA carboxylase), inhibiting fatty acid synthesis and favoring glucose uptake.
Recent studies (e.g., 2025 Nature article) confirm MOTS-c's role in pancreatic islets, where it boosts glycolytic enzymes like PFK1, preventing senescence.
- NAD+ Improvement and AMPK Synergy: MOTS-c elevates NAD+ levels by enhancing NAD+ salvage pathways and mitochondrial biogenesis via PGC-1α upregulation. Although AMPK activation typically depletes NAD+ in acute states, MOTS-c's chronic effects parallel NAD+ boosting (e.g., via SIRT1 activation), resolving the apparent paradox. This dual action supports mitochondrial repair and energy efficiency, as seen in 2025 NIH studies
showing restored OXPHOS and reduced ATP hydrolysis in damaged mitochondria.
- p53 Upregulation and NF-κB Downregulation: MOTS-c translocates to the nucleus, interacting with transcription factors to increase p53 expression, promoting DNA repair and apoptosis in stressed cells. Conversely, it suppresses NF-κB signaling, reducing pro-inflammatory cytokines like TNF-α and CRP. This anti-inflammatory profile is key for metabolic health, without elevating homocysteine or other markers, despite increased methylation (via methionine cycle modulation).
- Mitochondrial Damage Repair: MOTS-c improves mitochondrial function by increasing ROS in a controlled manner ( hormesis), enhancing OXPHOS capacity, and mitigating damage from aging or diabetes. 2025 Springer studies on diabetic cardiomyopathy show MOTS-c restores membrane potential and biogenesis, acting as a mitohormetic agent.
Metabolic and Physiological Benefits
MOTS-c's MoA extends to systemic effects, positioning it as a therapeutic for obesity, insulin resistance, and muscle health.
- Obesity Prevention and Body Recomposition: By activating AMPK, MOTS-c inhibits lipogenesis and promotes fat oxidation, preventing weight gain and liver fat accumulation (2025 Taylor & Francis study). It aids body recomposition by enhancing lean mass through myostatin inhibition, reducing muscle atrophy signals. This is particularly beneficial for age-related sarcopenia, where MOTS-c mimics exercise-induced muscle adaptations.
- Insulin Resistance Improvement: MOTS-c enhances insulin sensitivity via GLUT4 translocation and IRS-1 phosphorylation, countering resistance in type 2 diabetes models. In 2025 Nature research, it protected pancreatic islets in nonobese diabetic mice, improving glucose tolerance.
- Exercise Mimetic Properties: As an "exercise in a pill," MOTS-c replicates endurance training effects by boosting AMPK and PGC-1α, increasing mitochondrial density and aerobic capacity. 2025-2026 studies link exercise intensity to circulating MOTS-c levels, correlating with metabolic improvements.
- Methylation Effects Without Inflammatory Drawbacks: MOTS-c increases global DNA methylation by altering one-carbon metabolism, supporting epigenetic stability. However, it does not elevate inflammatory markers (CRP,TNF-α) or homocysteine, avoiding risks associated with hypermethylation therapies.
Similarities to Humanin and Applications in Neurodegeneration
MOTS-c exhibits Humanin-like effects, including neuroprotection and anti-apoptotic actions, but with a distinct structure (no shared sequence motifs) and administration routes (e.g., injectable vs. oral potential). In neurodegenerative diseases, MOTS-c modulates AMPK in neurons, reducing amyloid aggregation and tau phosphorylation. 2025 studies suggest applications in Alzheimer's, where it preserves synaptic function and mitochondrial integrity, differing from Humanin's IGFBP-3 binding.
Related research context
To explore how mitochondrial efficiency and metabolic signaling intersect with muscle performance and recovery research, see:
→ Muscle Growth & Regeneration: Research Perspectives
Product Description:
Source: PubChem
Este item é fornecido exclusivamente para fins de investigação.
Todas as informações fornecidas pela PRG destinam-se apenas a fins educativos e informativos.
Para manter a fiabilidade dos resultados laboratoriais, o armazenamento correto dos peptídeos é essencial. Condições adequadas ajudam a preservar a estabilidade dos peptídeos durante anos, protegendo-os contra contaminação, oxidação e degradação.
Embora alguns peptídeos sejam mais sensíveis do que outros, seguir estas boas práticas prolongará significativamente a vida útil e a integridade estrutural.
Os peptídeos podem ser comprometidos pela exposição à humidade e ao ar, especialmente após a remoção do congelador.
Os peptídeos em solução têm uma vida útil muito mais curta do que na forma liofilizada e são mais suscetíveis à degradação bacteriana.
Selecionar recipientes limpos, intactos, quimicamente resistentes e adequados ao volume da amostra.
Peptídeos enviados em frascos de plástico podem ser transferidos para vidro para armazenamento a longo prazo, se desejado.
