Finding the right organelle

The mitochondrial outer membrane contains a diverse set of proteins that includes enzymes, components of the preprotein translocation machinery, pore‐forming proteins, regulators of programmed cell death, and those that control the morphology of the organelle. All these proteins, like the vast majority of mitochondrial proteins, are encoded in the nucleus, so they are synthesized in the cytosol and contain signals that are essential for their subsequent import into mitochondria. This review summarizes our current knowledge of the signals that target mitochondrial outer‐membrane proteins to their correct intracellular location. In addition, the mechanisms by which these signals are decoded by the mitochondria are discussed.

[1]  A. Suzuki,et al.  aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization , 2002, Journal of Cell Science.

[2]  C. Thompson,et al.  bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria. , 1994, Development.

[3]  Reiner Hegerl,et al.  Tom40, the Pore-Forming Component of the Protein-Conducting Tom Channel in the Outer Membrane of Mitochondria , 2001, The Journal of cell biology.

[4]  W. Neupert,et al.  Specific recognition of mitochondrial preproteins by the cytosolic domain of the import receptor MOM72. , 1994, The Journal of biological chemistry.

[5]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[6]  R. Jensen,et al.  Protein import into and across the mitochondrial inner membrane: role of the TIM23 and TIM22 translocons. , 2002, Biochimica et biophysica acta.

[7]  N. Pfanner,et al.  Preprotein Translocase of the Outer Mitochondrial Membrane: Molecular Dissection and Assembly of the General Import Pore Complex , 1998, Molecular and Cellular Biology.

[8]  W. Neupert,et al.  Connection of the Mitochondrial Outer and Inner Membranes by Fzo1 Is Critical for Organellar Fusion , 2001, The Journal of cell biology.

[9]  T. Lithgow,et al.  Targeting of tail‐anchored proteins to yeast mitochondria in vivo , 1999, FEBS letters.

[10]  N. Pfanner,et al.  Versatility of the mitochondrial protein import machinery , 2001, Nature Reviews Molecular Cell Biology.

[11]  D. Rapaport Biogenesis of the mitochondrial TOM complex. , 2002, Trends in biochemical sciences.

[12]  H. McBride,et al.  A signal-anchor sequence selective for the mitochondrial outer membrane , 1992, The Journal of cell biology.

[13]  J. Gamble,et al.  A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal. , 1998, Molecular biology of the cell.

[14]  W. Neupert,et al.  Structural requirements of Tom40 for assembly into preexisting TOM complexes of mitochondria. , 2001, Molecular biology of the cell.

[15]  S. Colombo,et al.  The tale of tail-anchored proteins , 2003, The Journal of cell biology.

[16]  R. Maizels,et al.  Serine proteinase inhibitors from nematodes and the arms race between host and pathogen. , 2001, Trends in biochemical sciences.

[17]  K. Dietmeier,et al.  Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins , 1998, Nature.

[18]  N. Borgese,et al.  The specific subcellular localization of two isoforms of cytochrome b5 suggests novel targeting pathways. , 1993, The Journal of biological chemistry.

[19]  N. Pfanner,et al.  The three modules of ADP/ATP carrier cooperate in receptor recruitment and translocation into mitochondria , 2001, The EMBO journal.

[20]  W. Neupert,et al.  Import pathways of precursor proteins into mitochondria: multiple receptor sites are followed by a common membrane insertion site , 1988, The Journal of cell biology.

[21]  T. Lithgow,et al.  Targeting of C‐Terminal (Tail)‐Anchored Proteins: Understanding how Cytoplasmic Activities are Anchored to Intracellular Membranes , 2001, Traffic.

[22]  W. Neupert,et al.  Recognition of preproteins by the isolated TOM complex of mitochondria , 2000, The EMBO journal.

[23]  T. Lithgow,et al.  The alpha and the beta: protein translocation across mitochondrial and plastid outer membranes. , 2001, Trends in biochemical sciences.

[24]  R. Hegerl,et al.  The Tom Core Complex , 1999, The Journal of cell biology.

[25]  C E Lawrence,et al.  Detection of likely transmembrane β-strand regions in sequences of mitochondrial pore proteins using the Gibbs sampler , 1996, Journal of bioenergetics and biomembranes.

[26]  T. Lithgow,et al.  The protein import receptor of mitochondria. , 1995, Trends in biochemical sciences.

[27]  N. Pfanner,et al.  Multistep assembly of the protein import channel of the mitochondrial outer membrane , 2001, Nature Structural Biology.

[28]  E. Schleiff,et al.  Direct Membrane Insertion of Voltage-dependent Anion-selective Channel Protein Catalyzed by Mitochondrial Tom20 , 1999, The Journal of cell biology.

[29]  Maki Maeda,et al.  Characterization of rat TOM70 as a receptor of the preprotein translocase of the mitochondrial outer membrane. , 2002, Journal of cell science.

[30]  K. Mihara,et al.  Both amino- and carboxy-terminal portions are required for insertion of yeast porin into the outer mitochondrial membrane. , 1988, Journal of biochemistry.

[31]  S. Korsmeyer,et al.  Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence. , 1993, The Journal of biological chemistry.

[32]  T. Lithgow,et al.  A conserved proline residue is present in the transmembrane‐spanning domain of Tom7 and other tail‐anchored protein subunits of the TOM translocase , 2002, FEBS letters.

[33]  W. Neupert,et al.  Biogenesis of Porin of the Outer Mitochondrial Membrane Involves an Import Pathway via Receptors and the General Import Pore of the Tom Complex , 2001, The Journal of cell biology.

[34]  W. Neupert,et al.  Biogenesis of Tom40, Core Component of the Tom Complex of Mitochondria , 1999, The Journal of cell biology.

[35]  D. Andrews,et al.  Assembly of Bcl-2 into microsomal and outer mitochondrial membranes. , 1994, The Journal of biological chemistry.

[36]  W. Neupert,et al.  Role of the N‐ and C‐termini of porin in import into the outer membrane of Neurospora mitochondria , 1996, FEBS letters.

[37]  T. Ikenoue,et al.  Charged Amino Acids at the Carboxyl-Terminal Portions Determine the Intracellular Locations of Two Isoforms of Cytochromeb 5 * , 1998, The Journal of Biological Chemistry.

[38]  H. McBride,et al.  Import and insertion of proteins into the mitochondrial outer membrane. , 1995, European journal of biochemistry.

[39]  W. Neupert,et al.  Assembly of the Preprotein Receptor MOM72/MAS70 into the Protein Import Complex of the Outer Membrane of Mitochondria (*) , 1995, The Journal of Biological Chemistry.

[40]  C. Borner,et al.  Characterization of the signal that directs Bcl-xL, but not Bcl-2, to the mitochondrial outer membrane , 2003, The Journal of cell biology.

[41]  J. Shaw,et al.  Dnm1p Gtpase-Mediated Mitochondrial Fission Is a Multi-Step Process Requiring the Novel Integral Membrane Component Fis1p , 2000, The Journal of cell biology.

[42]  Joachim Rassow,et al.  Bcl-2 and porin follow different pathways of TOM-dependent insertion into the mitochondrial outer membrane. , 2002, Journal of molecular biology.

[43]  W. Neupert,et al.  Tom40 PLAYS A MAJOR ROLE IN TARGETING AND TRANSLOCATION OF PREPROTEINS BY FORMING A SPECIFIC BINDING SITE FOR THE PRESEQUENCE , 1997 .

[44]  D. Mokranjac,et al.  Protein import into mitochondria. , 2005, Biochemical Society transactions.

[45]  J. Schneider-Mergener,et al.  Distribution of Binding Sequences for the Mitochondrial Import Receptors Tom20, Tom22, and Tom70 in a Presequence-carrying Preprotein and a Non-cleavable Preprotein* , 1999, The Journal of Biological Chemistry.

[46]  K. Mihara,et al.  Characterization of the Signal That Directs Tom20 to the Mitochondrial Outer Membrane , 2000, The Journal of cell biology.

[47]  N. Pfanner,et al.  Mitochondrial protein import. , 1989, Biochimica et biophysica acta.

[48]  Walter Neupert,et al.  Protein Import into Mitochondria , 2004 .

[49]  T. Lithgow,et al.  Tom40, the import channel of the mitochondrial outer membrane, plays an active role in sorting imported proteins , 2003, The EMBO journal.

[50]  W. Neupert,et al.  A crucial role of the mitochondrial protein import receptor MOM19 for the biogenesis of mitochondria , 1994, The Journal of cell biology.

[51]  W. Neupert,et al.  Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa * , 2001, The Journal of Biological Chemistry.

[52]  W. Neupert,et al.  Targeting of the master receptor MOM19 to mitochondria. , 1991, Science.

[53]  B. Wattenberg,et al.  Targeting and insertion of C-terminally anchored proteins to the mitochondrial outer membrane is specific and saturable but does not strictly require ATP or molecular chaperones. , 2000, The Biochemical journal.

[54]  W. Neupert,et al.  Import pathways of precursor proteins into mitochondria , 1988 .

[55]  R. Benz,et al.  The Preprotein Translocation Channel of the Outer Membrane of Mitochondria , 1998, Cell.

[56]  N. Pfanner,et al.  Insertion of MOM22 into the mitochondrial outer membrane strictly depends on surface receptors , 1993, FEBS letters.

[57]  K. Mihara,et al.  Characterization of signal that directs C-tail-anchored proteins to mammalian mitochondrial outer membrane. , 2002, Molecular biology of the cell.

[58]  Trevor Lithgow,et al.  Bipartite Signals Mediate Subcellular Targeting of Tail-anchored Membrane Proteins in Saccharomyces cerevisiae * , 2003, The Journal of Biological Chemistry.