Revolutionary Discovery: New Insights into Mitochondrial Protein Import by Biochemists

Mitochondria are fascinating organelles in our cells. Think of them as tiny power plants that create ATP, the energy currency our cells use. These structures have a long history. They originated over a billion years ago when a simple cell formed a partnership with bacteria. Through time, mitochondria became crucial for our metabolism by depending on the host cell for most of their protein.

Recently, researchers at Caltech uncovered how mitochondrial proteins are transported from the ribosomes, which are the cell’s protein factories, to the mitochondria. This process is more complex than previously thought, mainly because it involves how proteins fold.

Shu-ou Shan, a chemistry professor at Caltech, explains, “It turns out that localizing proteins to mitochondria involves a multilayered, complex pathway.” Traditionally, scientists believed that mitochondrial proteins were only imported after they were fully synthesized. However, a new paper in Cell reveals that up to 20% of mitochondrial proteins can start their journey while they are still being made. This is called cotranslational import.

Zikun Zhu, the lead author of the paper, and his team found that larger, more complex proteins are prioritized in this transport process. These proteins have intricate folding patterns, essential for their function. If the proteins were allowed to fully form in the cytoplasm, they might get stuck, clogging the import channels in the mitochondria.

But how does a cell know which proteins to send to the mitochondria midway through their creation? The team discovered that these proteins carry a mitochondrial targeting sequence, like a signal to direct them. However, there’s a twist. Another signal, in the form of a large protein domain, is also necessary to trigger their transport during translation.

Zhu likens this to having a boarding pass locked in a suitcase. The targeting sequence is the pass, while the large domain is the code to open the suitcase. The team even showed that adding a large domain to other proteins could reroute them for co-import.

What does this mean for science? Understanding this process could provide insights into why cells have developed such a detailed targeting system for mitochondrial proteins. It could lead to new treatments and therapeutic applications by manipulating mitochondrial protein import.

This research is crucial, especially as interest in mitochondrial function grows. Mitochondria play a significant role in diseases like diabetes and neurodegenerative disorders. As we learn more about how proteins are transported, we can explore how to address these diseases more effectively.

For more on this topic, you can check out the full paper titled “Principles of cotranslational mitochondrial protein import” in the journal Cell here.

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