A summary of Mitochondrial-derived peptide MOTS-c suppresses ovarian cancer progression through the USP7/LARS1 axis. Advanced Science (2025)
For years, scientists have known that mitochondria do much more than produce energy. They’re increasingly recognized as key regulators of aging, metabolism, inflammation, and even cancer. One of the most intriguing molecules to emerge from mitochondrial research is MOTS-c, a naturally occurring peptide encoded within mitochondrial DNA.
A new study published in Advanced Science adds another piece to the puzzle, suggesting that MOTS-c may play an important role in slowing ovarian cancer growth by disrupting a pathway that cancer cells rely on to survive.
While the research is still in its early stages, the findings highlight another promising area where mitochondrial peptides could one day contribute to future cancer therapies.
What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a small peptide naturally produced inside mitochondria. Since its discovery in 2015, researchers have linked it to a variety of biological processes, including:
- Energy metabolism
- Insulin sensitivity
- Exercise performance
- Cellular stress responses
- Healthy aging
- Inflammation
More recently, scientists have begun investigating whether MOTS-c may also influence how cancer cells grow and survive.
What Did Researchers Discover?
In this study, researchers examined ovarian cancer cells, human tumor samples, and mouse models to better understand MOTS-c’s role.
Their findings were striking.
When ovarian cancer cells were treated with MOTS-c, researchers observed:
- Slower cancer cell growth
- Reduced tumor cell migration
- Decreased invasion into surrounding tissues
- Increased cancer cell death
- Significantly smaller tumors in animal models
Instead of simply reducing cellular energy production, MOTS-c appeared to interfere with one of the cancer cell’s most important survival systems.
How Does MOTS-c Work?
Cancer cells rely heavily on a protein called LARS1, which helps activate a major growth regulator known as mTOR.
The mTOR pathway acts like a master switch that tells cells when to grow, divide, and produce proteins. Many cancers become highly dependent on this pathway.
Normally, another protein called USP7 protects LARS1 from being broken down.
Researchers discovered that MOTS-c interrupts this process.
When MOTS-c reduces USP7 activity:
- LARS1 is no longer protected.
- LARS1 is broken down naturally.
- mTOR signaling decreases.
- Cancer cell growth slows.
Rather than attacking cancer cells directly, MOTS-c essentially removes one of the molecular supports they depend on.
Human Tumor Samples Supported the Findings
The research didn’t stop with laboratory experiments.
Scientists also analyzed ovarian tumor samples from patients.
They found that:
- Lower levels of MOTS-c were associated with poorer patient outcomes.
- Higher levels of USP7 and LARS1 were linked with more aggressive tumors.
These observations strengthen the possibility that MOTS-c plays a meaningful role in ovarian cancer biology.
Why This Matters
Ovarian cancer remains one of the most difficult gynecologic cancers to treat, largely because it is often diagnosed after it has already spread.
Finding new therapeutic targets is a major focus of ongoing research.
This study suggests that restoring or enhancing MOTS-c activity could eventually become one approach for disrupting the molecular pathways ovarian cancer cells use to survive.
Although much more work is needed before any clinical application, the discovery opens an exciting new direction for mitochondrial medicine and peptide research.
The Bottom Line
MOTS-c continues to demonstrate that mitochondrial peptides may influence far more than metabolism and healthy aging.
This study found that MOTS-c:
- Suppressed ovarian cancer growth in laboratory and animal studies.
- Reduced cancer cell migration and invasion.
- Blocked the USP7-LARS1-mTOR signaling pathway.
- Produced significantly smaller tumors in mice.
- Was associated with better outcomes when naturally present at higher levels in human tumor samples.
While these findings are promising, it’s important to remember that this research is preclinical. Human clinical trials will be necessary before MOTS-c can be considered as a potential treatment for ovarian cancer.
As our understanding of mitochondrial signaling continues to grow, peptides like MOTS-c are becoming increasingly important areas of biomedical research—not only for metabolism and longevity, but potentially for oncology as well.
Original Research
Zhao Y, et al. Mitochondrial-derived peptide MOTS-c suppresses ovarian cancer progression through the USP7/LARS1 axis. Advanced Science (2025).
https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202405620
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