Almost every human cell carries two sets of DNA. One sits in the nucleus. The other is a tiny loop inside the mitochondria, and that loop is where scientists found the first mitochondrial peptides. Most of us learned "powerhouse of the cell" in school and figured that was the whole story. It isn't.
Mitochondria write some of their own messages
For decades, scientists read the mitochondria's little genome as a parts list for the power plant itself. Then they found peptides hiding in it. A peptide is just a short chain of protein building blocks, and these ones work as signals for the rest of the cell. That changed the whole conversation.
The proof: how mitochondrial peptides were found
Here's what's actually going on.
Start with the power plant. Think of a cell as a small town and mitochondria as its power plants. They take in fuel and oxygen and turn out ATP, the molecule cells spend like cash. That's the part everyone remembers from biology class.
They carry their own DNA because they used to be bacteria. Scientists think mitochondria started out as free-living bacteria that moved into bigger cells more than a billion years ago (Youle, Science 2019). In 1981, Fred Sanger's team in Cambridge, England, read the whole human mitochondrial genome: 16,569 letters, with genes packed so tight there's barely a gap between them (Anderson et al., Nature 1981). It looked like a tidy parts list. No room for surprises.
Then the surprises showed up. In 2001, a team at Keio University in Tokyo found humanin, a short peptide that protected nerve cells in a dish from damage tied to Alzheimer's disease genes (Hashimoto et al., PNAS 2001). Its code matches a stretch of mitochondrial DNA. In 2015, a USC team found a second one, MOTS-c, 16 building blocks long, tucked inside a gene that was already known for a different job (Lee et al., Cell Metab 2015). Both have been studied mostly in cells and animals.
So why should you care? Because "mitochondrial peptide" gets used for two very different things. MOTS-c is made by mitochondria, and humanin's code matches the mitochondrial genome too. SS-31 was designed in a lab to act on them. Exactly one drug product made from it, elamipretide, got FDA accelerated approval in 2025 for one rare inherited disease, Barth syndrome (FDA, 2025). Research-grade SS-31 isn't FDA approved. So before you trust a claim on a page, check which kind of peptide it's about. (We put the two most talked-about ones side by side in MOTS-c vs SS-31.)
"Isn't NAD+ one of these?" Nope. NAD+ isn't a peptide at all. It's a small helper molecule mitochondria use to make energy. Same conversation, different kind of compound.
The big learning lesson
Keep reading: MOTS-c vs SS-31, compared side by side · How to read a peptide certificate of analysis · Peptide half-life explained
Frequently asked questions
What are mitochondrial peptides?
The term covers two groups. Some are coded in the mitochondria's own DNA, like MOTS-c and humanin. Others, like SS-31, were designed in a lab to act on mitochondria.
Do mitochondria have their own DNA?
Yes. It's a small loop of 16,569 DNA letters, separate from the DNA in the nucleus, likely left over from the bacteria mitochondria came from. MOTS-c is coded there, and humanin's code matches a stretch of it.
Is NAD+ a peptide?
No. NAD+ is a small helper molecule (a coenzyme) used in energy production. It comes up alongside mitochondrial peptides a lot, but it's a different kind of compound.