Pathways for the incorporation of polypeptides into mitochondria. A. Incorporation of matrix proteins. A targeting signal located within a cleavable
presequence at the N-terminus of the polypeptide (1) leads first to the association of the polypeptide first with the outer membrane (2) and then, in the
presence of a transmembrane potential (3), to the passage of the polypeptide into the matrix through a point of contact between the two membranes. In an
intermediate stage (4), parts of the polypeptide have reached the matrix while others are still exposed on the mitochondrial surface. The presequence is
removed by a matrix metalloprotease and (5) the final product may remain in the matrix (as is the case with ornithine transcarbamylase; OTC) or become
peripherally associated with the inner membrane (as is the case with the β subunit of the F1 ATPase). B. Incorporation of a protein into the outer
Source: The Biogenesis of Membranes and Organelles, The Online Metabolic and Molecular Bases of Inherited Disease
membrane. The polypeptide contains an N-terminal targeting signal that is immediately followed by a localization signal (1). As in A, the targeting signal
Citation: of
Valle
Beaudet AL,
Vogelstein
Kinzler KW,
Antonarakis
SE, Ballabio
A, Gibson
K, Mitchell
The Online
Metabolic
and Molecular
leads to association
theD,
polypeptide
with
the outerB,membrane
(2),
but the localization
signal
prevents
passageG.through
the inner
membrane
at the
Bases
of
Inherited
Disease;
2014
Available
at:
http://mhmedical.com/
Accessed:
July
31,
2017
contact point (3 and 4). The localization signal is a hydrophobic segment similar to the halt-transfer signal of type I membrane proteins. In the figure, the
Copyright
© 2017 protein
McGraw-Hill
Education.
All rightsinreserved
targeting signal
of the mature
is depicted
as exposed
the intermembrane space, but this has not been shown and the part of the protein that
forms an amphipathic helix may also be embedded in the outer membrane. The model is based on experimental data obtained for a 70-kDa outer