TY - JOUR
T1 - The GET pathway can increase the risk of mitochondrial outer membrane proteins to be mistargeted to the ER
AU - Vitali, Daniela G.
AU - Sinzel, Monika
AU - Bulthuis, Elianne P.
AU - Kolb, Antonia
AU - Zabel, Susanne
AU - Mehlhorn, Dietmar G.
AU - Costa, Bruna Figueiredo
AU - Farkas, Akos
AU - Clancy, Anne
AU - Schuldiner, Maya
AU - Grefen, Christopher
AU - Schwappach, Blanche
AU - Borgese, Nica
AU - Rapaport, Doron
N1 - We thank E. Kracker for excellent technical assistance and Irmgard Sinning, Biochemistry Center (BZH), Heidelberg, Germany, for plasmids. Author contributions Conceptualization: D.G.V., C.G., B.S., N.B., D.R.; Methodology: D.G.V., E.P.B., M. Sinzel, A.K., S.Z., D.G.M., A.C., A.F., B.F.C., C.G., D.R.; Formal analysis: D.R.; Investigation: D.G.V., E.P.B., M. Sinzel, A.K., S.Z., A.C., B.F.C., C.G.; Resources: A.C., A.F., M. Schuldiner, B.S., N.B., D.R.; Data curation: E.P.B., M. Sinzel, A.K., S.Z., D.G.M., C.G.; Writing - original draft: D.G.V., M. Schuldiner, B.S., N.B., D.R.; Writing - review & editing: C.G.; Supervision: B.S., N.B., D.R. Funding This work was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 1190-TP04 to B.S.; RA 1028/7-1 to D.R.; DeutschIsraelische Projektkooperation to D.R. and M. Schuldiner; and GR 4251/2-1 to C.G.), and the ITN TAMPting network to D.G.V., B.F.C., B.S., N.B. and D.R. [funded by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/ under REA grant agreement no 607072].
PY - 2018/5/15
Y1 - 2018/5/15
N2 - Tail-anchored (TA) proteins are anchored to their corresponding membrane via a single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial TA proteins are targeted to their destination. It has been widely observed that some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when overexpressed or when their targeting signal is masked. However, the mechanism of this erroneous sorting is currently unknown. In this study, we demonstrate the involvement of the GET machinery in the mistargeting of suboptimal MOM proteins to the ER. These findings suggest that the GET machinery can, in principle, recognize and guide mitochondrial and non-canonical TA proteins. Hence, under normal conditions, an active mitochondrial targeting pathway must exist that dominates the kinetic competition against other pathways.
AB - Tail-anchored (TA) proteins are anchored to their corresponding membrane via a single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial TA proteins are targeted to their destination. It has been widely observed that some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when overexpressed or when their targeting signal is masked. However, the mechanism of this erroneous sorting is currently unknown. In this study, we demonstrate the involvement of the GET machinery in the mistargeting of suboptimal MOM proteins to the ER. These findings suggest that the GET machinery can, in principle, recognize and guide mitochondrial and non-canonical TA proteins. Hence, under normal conditions, an active mitochondrial targeting pathway must exist that dominates the kinetic competition against other pathways.
UR - http://www.scopus.com/inward/record.url?scp=85047207752&partnerID=8YFLogxK
U2 - 10.1242/jcs.211110
DO - 10.1242/jcs.211110
M3 - مقالة
SN - 0021-9533
VL - 131
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 10
M1 - jcs211110
ER -