A cytosolic complex for targeting proteins to mitochondria
Nick Hoogenraad

A Cytosolic Complex for Targeting Proteins to Mitochondria

Nick Hoogenraad, Department of Biochemistry, La Trobe University, Victoria, 3086, Australia

Mitochondria from mammalian cells contain about 1500 different proteins. All but 12 of these are nuclear encoded, synthesized in the cytosol and imported into the mitochondrion (Hoogenraad et al, 2002). In order to pass through the mitochondrial import pore, these proteins have to be largely unfolded. Although this unfolding occurs predominantly through the force applied by the mitochondrial Hsp70, associated with the inner face of the mitochondrial inner membrane (“molecular ratchet”), the highly hydrophobic integral membrane proteins of the outer and inner membranes of the organelle cannot avail themselves of this force applied from the matrix of the mitochondrion. These proteins require the assistance of molecular chaperones Hsp90 and Hsp70 in the cytosol to maintain them in an import competent conformation (Young et al, 2003).

We have found that these chaperones are part of an import complex (an “importasome”) which transfers mitochondrial proteins from the ribosome to the translocation complex of the outer membrane (TOM Complex).This complex docks with a receptor of 70kDa (TOM70) via an interaction of the carboxy-terminal acid domain of the chaperones with a TPR clamp domain on the receptor.

I will discuss the molecular nature of the cytosolic targeting complex and the role of this complex in protein targeting and import .

References:

Hoogenraad, N.J., Ward, L.A. & Ryan, M.T. (2002). Import and assembly of proteins into mitochondria from mammalian cells. Biochim Biophys Acta 1592, 97-105.
Young, J.C., Hoogenraad, N.J. & Hartl, F.U. (2003). Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112, 1-20.