Mitochondrial Protein Import

Aug. 30, 2025

Recently, researchers at Caltech University have uncovered new rules governing mitochondrial protein import, revising the long-standing understanding of how proteins are transported into mitochondria.

About Mitochondria

  • Mitochondria are double-membraned organelles that generate ATP (adenosine triphosphate), the universal cellular energy currency.
  • They originated over a billion years ago through endosymbiosis between a primitive archaeal cell and a bacterium.
  • Over time, mitochondria transferred most of their genes to the host nucleus, making them dependent on the host cell for protein supply.

Traditional Model of Protein Import

  • Earlier, it was believed that mitochondrial proteins are imported only after translation is completed in the cytosol.
  • Proteins were thought to fully synthesize on ribosomes before passing through mitochondrial membrane channels.

New Findings by Caltech Scientists

  • Around 20% of mitochondrial proteins are cotranslationally imported, i.e., they are imported while still being synthesized by ribosomes.
  • This mechanism mainly applies to large and structurally complex proteins that require assistance during folding.
  • If these proteins fully fold in the cytosol, they risk forming irreversible structures that block import channels.

Mechanism of Cotranslational Import

  • Such proteins contain a mitochondrial targeting sequence, but this alone is insufficient for cotranslational delivery.
  • A second signal is required – the first large protein domain that emerges during translation.
  • This domain acts like a “code to unlock the boarding pass”, ensuring the protein is guided into mitochondria early.
  • Experiments confirmed that transplanting these domains onto other proteins rerouted them for cotranslational import.

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