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Medizin - Open Access LMU - Teil 11/22 Podcast
The requirement of matrix ATP for the import of precursor proteins into the mitochondrial matrix and intermembrane space

The requirement of matrix ATP for the import of precursor proteins into the mitochondrial matrix and intermembrane space

Medizin - Open Access LMU - Teil 11/22 vor 32 Jahren

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The role of ATP in the matrix for the import of precursor proteins
into the various mitochondrial subcompartments was investigated by
studying protein translocation at experimentally defined ATP
levels. Proteins targeted to the matrix were neither imported or
processed when matrix ATP was depleted. Import and processing of
precytochrome b2, (pb2), a precursor carrying a bipartite
presequence, into the intermembrane space was also strongly
dependent on matrix ATP. Preproteins, consisting of 220 or more
residues of pb2 fused to dihydrofolate reductase, showed the same
requirement for matrix ATP, whereas the import of shorter fusion
proteins (up to 167 residues of pb2) was largely independent of
matrix ATP. For those intermembrane-space-targeted proteins that
did need matrix ATP, the dependence could be relieved either by
unfolding these proteins prior to import or by introducing a
deletion into the mature portion of the protein thereby impairing
the tight folding of the cytochrome b5 domain. These results
suggest the following: (a) The import of matrix-targeted
preproteins, in addition to a membrane potential ΔΨ, requires
matrix ATP [most likely to facilitate reversible binding of
mitochondrial heat-shock protein 70 (mt-Hsp70) to incoming
precursors], for two steps, securing the presequence on the matrix
side of the inner membrane and for the completion of translocation;
(b) in the case of intermembrane-space-targeted precursors with
bipartite signals, the function of ATP/mt-Hsp70 is not obligatory,
as components of the intermembrane-space-sorting pathway may
substitute for ATP/mt-Hsp70 function (however, if a tightly folded
domain is present in the precursor, ATP/mt-Hsp70 is indispensable);
(c) unfolding on the mitochondrial surface of tightly folded
segments of preproteins is facilitated by matrix-ATP/mt-Hsp70.