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Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane

H Koll1, B Guiard, J Rassow

  • 1Institut für Physiologische Chemie, München, Germany.

Cell
|March 20, 1992
PubMed

Insights

Mitochondrial protein cytochrome b2 uses hsp60 to control its folding and export. An export sequence in cytochrome b2 acts as a switch, regulating protein transport between mitochondrial compartments.

Area of Science:

  • Mitochondrial protein import and export
  • Molecular chaperones and protein folding
  • Cellular transport mechanisms

Background:

  • Cytochrome b2 is imported into mitochondria via the matrix and then exported to the intermembrane space.
  • Hsp60, a molecular chaperone, interacts with cytochrome b2 in the matrix, arresting its folding before export.
  • The bacterial-type export sequence in pre-cytochrome b2 plays a crucial role in regulating this process.

Purpose of the Study:

  • To elucidate the mechanism by which cytochrome b2 is transported to the mitochondrial intermembrane space.
  • To investigate the role of hsp60 and the export sequence in controlling protein folding and export.
  • To understand how proteins are channeled between import and export machineries in mitochondria.

Main Methods:

  • Analysis of protein transport pathways in mitochondria.
  • Investigating the interaction between cytochrome b2, hsp60, and the mitochondrial export machinery.
  • Studying the function of the bacterial-type export sequence in pre-cytochrome b2.

Main Results:

  • Hsp60 arrests cytochrome b2 folding in the matrix, facilitating its subsequent export.
  • The export sequence inhibits ATP-dependent release from hsp60, requiring inner membrane machinery interaction for export.
  • Export can initiate before complete import, dependent on a critical polypeptide length in the matrix.
  • Hsp60 exhibits dual activity: promoting matrix protein folding and maintaining unfolded states for transport.

Conclusions:

  • Hsp60 acts as a crucial regulator, balancing protein folding for matrix destination and maintaining unfolded states for inter-compartmental transport.
  • The anti-folding export sequence in cytochrome b2 functions as a molecular switch, directing protein traffic between mitochondrial compartments.
  • This mechanism highlights a sophisticated interplay between chaperones and specific sequence elements in controlling protein localization within the mitochondria.

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