MOTS-c
mitochondrial function research
MOLECULAR FORMULA
C101H152N28O22S2
MOLECULAR WEIGHT
2174.6 U
RESEARCH CATEGORY
MITOCHONDRIAL FUNCTION RESEARCH
RESEARCH DATA
PEER REVIEWED
MOTS-c, or Mitochondrial Open Reading Frame of the 12S rRNA-c, is a 16-amino-acid peptide encoded within the mitochondrial genome, specifically from the 12S rRNA gene. Its full chemical name is Methionyl-Arginyl-Glutamyl-Isoleucyl-Glutamyl-Phenylalanyl-Isoleucyl-Glutaminyl-Tryptophyl-Leucyl-Methionyl-Arginyl-Glycyl-Lysyl-Tyrosine-Lysine (MRWQEMGYIFYPRKLR), a sequence uniquely derived from an open reading frame rather than nuclear DNA, distinguishing it as a mitochondrial-derived peptide (MDP). This short peptide features a mix of polar and hydrophobic residues, contributing to its bioactive stability and signaling role in cellular metabolism.
MOTS-c is a tiny protein made in the powerhouses of cells (mitochondria) rather than the cell's command center (nucleus). It's a string of 16 building blocks that help cells manage energy, which makes it special because most proteins come from different instructions in the cell.
Yes, MOTS-c is primarily known as Mitochondrial Open Reading Frame of the 12S rRNA-c, often abbreviated in literature as MOTS-c or MDP-MOTS-c to emphasize its mitochondrial origin among other mitochondrial-derived peptides. It lacks widely recognized synonyms beyond these designations, though some studies refer to it descriptively as a 'mitochondrial signaling peptide' or 'mitokine' due to its role in intercellular communication. The term 'MOTS-c' remains the standard in peer-reviewed research, reflecting its specific genetic locus and function.
MOTS-c goes by its full name "Mitochondrial Open Reading Frame of the 12S rRNA-c" or just MOTS-c for short. Sometimes it's called MDP-MOTS-c to show it's from mitochondria. Some researchers call it a "mitokine" because it helps cells talk to each other, but most scientists stick with MOTS-c in their papers.
Emerging trends in MOTS-c research highlight its potential as a metabolic regulator with implications beyond mitochondrial function. Hypotheses suggest it may enhance exercise performance and muscle metabolism by mimicking some effects of physical activity through AMP-activated protein kinase (AMPK) activation. Studies also explore its role in aging and longevity, proposing it could mitigate age-related insulin resistance or sarcopenia by improving mitochondrial bioenergetics. Additionally, there's growing interest in its anti-inflammatory properties and possible neuroprotective effects via modulation of oxidative stress, though these applications remain preclinical and require extensive mechanistic and translational studies to confirm efficacy.
Scientists are getting excited about MOTS-c—it's like a tiny power-up from your cells' energy factories! They're guessing it could boost your workout game, keep muscles strong as you age, or even fight off inflammation and brain wear-out. Picture it as a secret helper for staying spry and sharp—big ideas still being cooked in the lab!
MOTS-c interacts primarily with the AMPK pathway, a key metabolic sensor, activating it independently of exercise to enhance glucose uptake and fatty acid oxidation in skeletal muscle. It also engages the sirtuin-1 (SIRT1) pathway, potentially amplifying mitochondrial biogenesis alongside nuclear-encoded regulators like PGC-1α. Studies suggest indirect effects on insulin signaling via improved mitochondrial function, though it doesn't bind insulin receptors directly. No significant interactions with non-metabolic systems (e.g., immune or cardiovascular) are well-documented, but its influence on cellular redox states hints at broader physiological crosstalk yet to be fully explored.
MOTS-c is like a backstage coach—it flips on AMPK, the body's energy manager, to help muscles use sugar and fat better, no workout needed! It also chats with SIRT1, a longevity switch, to boost energy factories in cells. It might nudge insulin's game indirectly, but it's mostly a metabolism maestro with secrets still unfolding!
In mouse studies, MOTS-c (5 mg/kg/day, intraperitoneal) increases insulin sensitivity by 20–30% and enhances glucose uptake in skeletal muscle by 1.5- to 2-fold within 7 days (Lee et al., 2015). It also boosts endurance capacity by 25–40% in aged mice, mimicking exercise effects. In cell cultures, it upregulates PGC-1α expression by 2-fold, enhancing mitochondrial function (Lee et al., 2015). No direct IGF-1 modulation is reported, as its effects are metabolic rather than growth-factor-driven, highlighting its potency in energy homeostasis.
In lab mice, MOTS-c is a metabolism champ—a 5 mg/kg shot daily bumps insulin sensitivity 20–30% and sugar use in muscles 1.5 to 2 times in a week (Lee et al., 2015)! Older mice ran 25–40% longer, like they'd been hitting the gym. It's like a turbo boost for cell energy, doubling key signals—pretty impressive stats!
MOTS-c is designated for research use only, with standard warnings: 'Not for human consumption,' 'For laboratory use only,' and requiring IRB/IACUC oversight. No specific contraindications beyond these are noted in literature, as toxicity is minimal at studied doses (up to 15 mg/kg in mice). Its metabolic potency suggests careful monitoring in studies involving energy balance, but no evidence-based restrictions beyond regulatory guidelines apply.
MOTS-c is a lab-only star—big signs say 'No humans allowed!' and it's just for science fun. It's safe in studies so far, but its energy powers mean researchers keep a sharp eye—no scary warnings, just stick to the science playbook!
Reconstitute MOTS-c in sterile saline or bacteriostatic water at 1 mg/mL under aseptic conditions for solubility and stability. Store lyophilized powder at -20°C and reconstituted solution at 2–8°C, avoiding freeze-thaw cycles to preserve its peptide structure. Use within 4 weeks post-reconstitution, and handle with low-protein-binding materials to prevent loss—its mitochondrial origin makes it sensitive to degradation.
Mix MOTS-c with clean saltwater to make a 1 mg/mL potion—keep it germ-free! Freeze the dry stuff at -20°C like a tiny energy crystal, chill the mix in the fridge, and use it within a month. Handle it gently with special tools—it's a delicate cell booster!
No clinical trials or human research exist for MOTS-c as of February 2025; its evaluation is limited to preclinical models (e.g., mice) and in vitro studies. Initial discoveries (Lee et al., 2015) remain in the preclinical phase, with no registered human trials on ClinicalTrials.gov. Human safety and efficacy data are pending further translational research.
MOTS-c is still an animal lab hero—no human adventures yet! It's wowed mice and petri dishes since its big debut (Lee et al., 2015), but it's waiting for the safety green light to star in people tests—think of it as a rising star in the making!
MOTS-c primarily affects skeletal muscle, enhancing glucose uptake and mitochondrial function via AMPK and SIRT1 activation. It also influences adipose tissue, promoting fat oxidation, and may impact liver metabolism indirectly through systemic energy balance. Minimal direct effects on brain or heart are noted in preclinical models, though its role in reducing oxidative stress suggests potential neuronal benefits under investigation (Lee et al., 2015).
MOTS-c is a muscle and fat maestro—it revs up sugar use and energy in muscles, melts fat a bit, and might tweak liver fuel flow! It's mostly quiet on brain or heart, but could shield nerves from wear—it's like a targeted energy DJ with a few bonus tracks!
In mice, MOTS-c (5 mg/kg/day) improves insulin sensitivity by 20–30% and boosts endurance by 25–40% in aged models (Lee et al., 2015). In obese mice, it reduces fat mass by 10–15% over 10 days at 15 mg/kg/day, enhancing metabolic flexibility. Its effects are consistent across young and aged cohorts, suggesting broad applicability in metabolic research.
In mice, MOTS-c shines—insulin gets 20–30% sharper, and old mice run 25–40% longer with a 5 mg/kg shot (Lee et al., 2015)! Fat mice slim down 10–15% in 10 days—it's like a fitness coach in a tiny package, rocking energy across ages!
Future MOTS-c research may explore its potential as an exercise mimetic for conditions like sarcopenia or type 2 diabetes, leveraging its AMPK activation. Its role in aging and neuroprotection could be tested in longevity models or neurodegenerative disease studies. Synergy with mitochondrial-targeted therapies or metabolic enhancers (e.g., metformin) offers another avenue, though human translation remains a key focus.
What's next for MOTS-c? Maybe it's a gym buddy for weak muscles or diabetes, or a brain-shield for aging! Scientists might pair it with energy boosters or test it in people—it's like a tiny hero ready for bigger quests!
Tested in mouse models (e.g., young, aged, obese) and in vitro cell cultures (e.g., skeletal muscle, hepatocytes); no human trials reported (Lee et al., 2015).
MOTS-c's been a lab hit in mice—young, old, chubby—and in petri dishes with muscle and liver cells (Lee et al., 2015)! No human spotlight yet—it's still warming up for the big stage!
No formal LD50 data exists; studies report no toxicity at doses up to 15 mg/kg/day in mice over 10 days, with no organ damage observed (Lee et al., 2015). High tolerability is noted.
No 'danger limit' yet—mice take 15 mg/kg daily like champs with no harm (Lee et al., 2015)! It's a safety rockstar so far!
MOTS-c activates AMPK, enhancing phosphorylation at Thr172, which upregulates glucose transporter 4 (GLUT4) translocation to the cell membrane and increases fatty acid oxidation. It also boosts SIRT1 and PGC-1α expression, promoting mitochondrial biogenesis—no direct receptor binding, acting as a signaling peptide from mitochondria to nucleus (Lee et al., 2015).
MOTS-c flips an energy switch (AMPK) to pull sugar into muscles and burn fat, like a cellular power-up! It sparks SIRT1 and PGC-1α to build more energy factories—no VIP receptor, just a mitochondrial megaphone!
MOTS-c sharpens sugar use, melts fat, turbocharges cell energy, and calms wear-and-tear stress—like a metabolism makeover (Lee et al., 2015)!
Safe at studied doses (up to 15 mg/kg in mice) with no adverse effects reported (Lee et al., 2015); no human safety data available.
At lab doses, MOTS-c's smooth—no trouble in mice up to 15 mg/kg (Lee et al., 2015)! No human tales yet—it's a safe bet for now!
Intraperitoneal or subcutaneous injection at 1 mg/mL in saline; typical mouse doses 5–15 mg/kg/day (Lee et al., 2015). Store at 2–8°C post-reconstitution.
Inject MOTS-c in the belly or under skin after mixing with saltwater—5–15 mg/kg for mice rocks it (Lee et al., 2015)! Chill it in the fridge!
No significant adverse effects reported in mice at 15 mg/kg/day (Lee et al., 2015); no human data available.
No oopsies in mice at 15 mg/kg—smooth sailing (Lee et al., 2015)! Humans? No scoop yet!
MOTS-c increases insulin sensitivity by 20–30% and endurance by 25–40% in mice (Lee et al., 2015); in vitro, doubles PGC-1α expression.
MOTS-c boosts insulin 20–30% and stamina 25–40% in mice, doubles energy signals in dishes—science gold (Lee et al., 2015)!
Limited to preclinical data; no human studies, small sample sizes, long-term effects uncharted (Lee et al., 2015).
Only mouse tales—no human scoop, tiny groups, and long-term mysteries (Lee et al., 2015)!
Improves mitochondrial function, enhances insulin sensitivity, may reduce age-related metabolic decline (Lee et al., 2015).
MOTS-c tunes up energy factories, sharpens sugar use, might slow aging's energy slump (Lee et al., 2015)!
In vitro: 2-fold PGC-1α increase; in vivo: 20–30% insulin sensitivity boost, 25–40% endurance gain (Lee et al., 2015).
In dishes, doubles energy signals; in mice, lifts insulin 20–30% and stamina 25–40%—lab magic (Lee et al., 2015)!
5–15 mg/kg/day in mice (Lee et al., 2015).
5–15 mg/kg shots for mice—tiny energy kicks (Lee et al., 2015)!
Long-term safety, human efficacy, broader physiological impacts.
What happens years later? How's it in people or beyond metabolism? Big questions!
Targets AMPK, upregulates GLUT4 and PGC-1α via SIRT1 (Lee et al., 2015).
Hits AMPK, cranks sugar movers and energy builders—cellular wizardry (Lee et al., 2015)!
Synergy with exercise, metformin, or mitochondrial therapies.
Pair with workouts, diabetes pills, or cell energy boosters—future teamwork dreams!
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