Structural Features Within the Nascent Chain Regulate Alternative Targeting of Secretory Proteins to Mitochondria

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2013 Mar 14

PMID 23481258

Citations 21

Authors

Natalie V Pfeiffer

Daniela Dirndorfer

Sven Lang

Ulrike K Resenberger

Lisa M Restelli

Charles Hemion

Margit Miesbauer

Stephan Frank

Albert Neutzner

Richard Zimmermann

Konstanze F Winklhofer

Jorg Tatzelt

Affiliations

Soon will be listed here.

Abstract

Protein targeting to specified cellular compartments is essential to maintain cell function and homeostasis. In eukaryotic cells, two major pathways rely on N-terminal signal peptides to target proteins to either the endoplasmic reticulum (ER) or mitochondria. In this study, we show that the ER signal peptides of the prion protein-like protein shadoo, the neuropeptide hormone somatostatin and the amyloid precursor protein have the property to mediate alternative targeting to mitochondria. Remarkably, the targeting direction of these signal peptides is determined by structural elements within the nascent chain. Each of the identified signal peptides promotes efficient ER import of nascent chains containing α-helical domains, but targets unstructured polypeptides to mitochondria. Moreover, we observed that mitochondrial targeting by the ER signal peptides correlates inversely with ER import efficiency. When ER import is compromised, targeting to mitochondria is enhanced, whereas improving ER import efficiency decreases mitochondrial targeting. In conclusion, our study reveals a novel mechanism of dual targeting to either the ER or mitochondria that is mediated by structural features within the nascent chain.

Citing Articles

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