Targeting and Function of the Mitochondrial Fission Factor GDAP1 Are Dependent on Its Tail-Anchor
Open Access
- 2 April 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (4), e5160
- https://doi.org/10.1371/journal.pone.0005160
Abstract
Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM) by their carboxyl-terminal tail-anchor domain (TA). However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa). Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD) that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects.This publication has 28 references indexed in Scilit:
- The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian CellsMolecular Biology of the Cell, 2008
- An Artificial Mitochondrial Tail Signal/Anchor Sequence Confirms a Requirement for Moderate Hydrophobicity for TargetingBioscience Reports, 2007
- Cell-free analysis of tail-anchor protein targeting to membranesMethods, 2007
- A Lethal Defect of Mitochondrial and Peroxisomal FissionThe New England Journal of Medicine, 2007
- Identification of a Targeting Factor for Posttranslational Membrane Protein Insertion into the ERCell, 2007
- Unassisted translocation of large polypeptide domains across phospholipid bilayersThe Journal of cell biology, 2006
- Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteinsThe EMBO Journal, 2006
- The tale of tail-anchored proteinsThe Journal of cell biology, 2003
- The human dynamin‐related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter‐membrane spaceFEBS Letters, 2002
- Charged Amino Acids at the Carboxyl-Terminal Portions Determine the Intracellular Locations of Two Isoforms of Cytochromeb 5Published by Elsevier BV ,1998