Nature’s Boarding Pass: How Proteins Enter Mitochondria
Scientists Reveal Exciting New Rules for Mitochondrial Protein Delivery.
Caltech researchers have discovered a whole new layer in how proteins get to mitochondria, the energy centers of our cells. This finding challenges long-held beliefs and offers a glimpse into nature’s clever engineering.
For decades, scientists believed that mitochondrial proteins were made completely before being delivered. But the new study, published in Cell, shows that nearly 20 percent of these proteins begin their journey while still being made by ribosomes. This early delivery is called cotranslational import.
What makes this pathway special? The proteins that use it are usually large, complex, multi‑domain molecules, the kind that are difficult to fold correctly if fully formed out in the cell fluid. Folding them early and sending them off right away helps prevent them from getting stuck or forming tangled knots that could clog the mitochondrial gates.
But how does the cell know which proteins need this special route? It turns out there’s a two step signal system at play:
- A mitochondrial targeting sequence (think of it like a boarding pass).
- The appearance of a large folded domain the ‘code’ that unlocks the suitcase so the boarding pass can be used.
As Zikun Zhu, the lead author, puts it: “It’s like having your boarding pass locked in a suitcase. The targeting sequence is the boarding pass, but to access it you need the code to open the suitcase. In this case, the large domain is that code.”
In fact, when the researchers added one of these large domains to proteins usually imported later, they redirected them to the cotranslational pathway showing just how powerful this signal really is.
Unlike cotranslational targeting in other cell parts, mitochondrial targeting happens later only after the big domain is ready. This strategy ensures only the right proteins enter at the right time.
Looking ahead, the team plans to dive deeper into how this system works at a molecular level with hopes of one day tuning it for medical or biotechnological applications.
The topic will be further discussed at the World Mitochondria Society (WMS) annual meeting in Berlin, October 2025, where leading experts will explore how such discoveries are shaping the future of mitochondrial medicine.
