TY - JOUR
T1 - The mitochondrial targeting sequence tilts the balance between mitochondrial and cytosolic dual localization
AU - Regev-Rudzki, Neta
AU - Yogev, Ohad
AU - Pines, Ophry
PY - 2008/7/15
Y1 - 2008/7/15
N2 - Dual localization of proteins in the cell has appeared in recent years to be a more abundant phenomenon than previously reported. One of the mechanisms by which a single translation product is distributed between two compartments, involves retrograde movement of a subset of processed molecules back through the organelle-membrane. Here, we investigated the specific contribution of the mitochondrial targeting sequence (MTS), as a cis element, in the distribution of two proteins, aconitase and fumarase. Whereas the cytosolic presence of fumarase is obvious, the cytosolic amount of aconitase is minute. Therefore, we created (1) MTS-exchange mutants, exchanging the MTS of aconitase and fumarase with each other as well as with those of other proteins and, (2) a set of single mutations, limited to the MTS of these proteins. Distribution of both proteins is affected by mutations, a fact particularly evident for aconitase, which displays extraordinary amounts of processed protein in the cytosol. Thus, we show for the first time, that the MTS has an additional role beyond targeting: it determines the level of retrograde movement of proteins back into the cytosol. Our results suggest that the translocation rate and folding of proteins during import into mitochondria determines the extent to which molecules are withdrawn back into the cytosol.
AB - Dual localization of proteins in the cell has appeared in recent years to be a more abundant phenomenon than previously reported. One of the mechanisms by which a single translation product is distributed between two compartments, involves retrograde movement of a subset of processed molecules back through the organelle-membrane. Here, we investigated the specific contribution of the mitochondrial targeting sequence (MTS), as a cis element, in the distribution of two proteins, aconitase and fumarase. Whereas the cytosolic presence of fumarase is obvious, the cytosolic amount of aconitase is minute. Therefore, we created (1) MTS-exchange mutants, exchanging the MTS of aconitase and fumarase with each other as well as with those of other proteins and, (2) a set of single mutations, limited to the MTS of these proteins. Distribution of both proteins is affected by mutations, a fact particularly evident for aconitase, which displays extraordinary amounts of processed protein in the cytosol. Thus, we show for the first time, that the MTS has an additional role beyond targeting: it determines the level of retrograde movement of proteins back into the cytosol. Our results suggest that the translocation rate and folding of proteins during import into mitochondria determines the extent to which molecules are withdrawn back into the cytosol.
KW - Aconitase
KW - Distribution
KW - Dual-localization
KW - Fumarase
KW - Mitochondrial-targeting-sequence
UR - http://www.scopus.com/inward/record.url?scp=49649109965&partnerID=8YFLogxK
U2 - 10.1242/jcs.029207
DO - 10.1242/jcs.029207
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C2 - 18577574
AN - SCOPUS:49649109965
SN - 0021-9533
VL - 121
SP - 2423
EP - 2431
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 14
ER -