I. Arnold et al., 2 DISTINCT AND INDEPENDENT MITOCHONDRIAL TARGETING SIGNALS FUNCTION IN THE SORTING OF AN INNER MEMBRANE-PROTEIN, CYTOCHROME C(1), The Journal of biological chemistry, 273(3), 1998, pp. 1469-1476
Proteins of the mitochondrial inner membrane display a wide variety of
orientations, many spanning the membrane more than once, Some of thes
e proteins are synthesized with NH2-terminal cleavable targeting seque
nces (presequences) whereas others are targeted to mitochondria via in
ternal signals, Here we report that two distinct mitochondrial targeti
ng signals can be present in precursors of inner membrane proteins, an
NH2-terminal one and a second, internal one, Using cytochrome c(1) as
a model protein, we demonstrate that these two mitochondrial targetin
g signals operate independently of each other, The internal targeting
signal, consisting of a transmembrane segment and a stretch of positiv
ely charged amino acid residues directly following it, initially direc
ts the translocation of the preprotein into the intermembrane space, I
t then inserts into the inner membrane from the intermembrane space si
de in a Delta psi-dependent manner and thereby determines the orientat
ion the protein attains in the inner membrane, Analysis of a number of
other presequence-containing protein of the inner membrane suggest th
at they too contain such internal targeting signals.