Apocytochrome c: an exceptional mitochondrial precursor protein using an exceptional import pathway

Stuart, Rosemary A.; Neupert, Walter

doi:10.1016/0300-9084(90)90136-5

Cited by 83 publications

(47 citation statements)

References 69 publications

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“…Thus, once C2Asig associates with the membrane, attachment of this hydrophobic ligand might aid its export across the CM in the absence of a signal peptide. In eucaryotes, after apocyt c binds to the mitochondrial OM, it serves as a substrate for the cyt c heme lyase (35), and subsequent heme attachment is believed to induce a conformational change that facilitates translocation across the OM. If heme was attached to C2Asig in the R. sphaeroides CM, then a similar conformational change could facilitate its export to the periplasm.…”

Section: Discussionmentioning

confidence: 99%

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The Rhodobacter sphaeroides cytochrome c2 signal peptide is not necessary for export and heme attachment

Brandner

Donohue

1994

J Bacteriol

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Rhodobacter sphaeroides cytochrome c2 (cyt c2) is a member of the heme-containing cytochrome c protein family that is found in the periplasmic space of this gram-negative bacterium. This exported polypeptide is made as a higher-molecular-weight precursor with a typical procaryotic signal peptide. Therefore, cyt c2 maturation is normally expected to involve precursor translocation across the cytoplasmic membrane, cleavage of the signal peptide, and covalent heme attachment. Surprisingly, synthesis as a precursor polypeptide is not a prerequisite for cyt c2 maturation because deleting the entire signal peptide does not prevent export, heme attachment, or function. Although cytochrome levels were reduced about threefold in cells containing this mutant protein, steady-state cyt c2 levels were significantly higher than those of other exported bacterial polypeptides which contain analogous signal peptide deletions. Thus, this mutant protein has the unique ability to be translocated across the cytoplasmic membrane in the absence of a signal peptide. The covalent association of heme with this mutant protein also suggests that the signal peptide is not required for ligand attachment to the polypeptide chain. These results have uncovered some novel aspects of bacterial c-type cytochrome biosynthesis.

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Section: Discussionmentioning

confidence: 99%

“…tional signal peptide for membrane translocation or whether, as in the case of mitochondrial cyt c, which is imported into mitochondria without a signal peptide, sequences within the mature polypeptide could also facilitate targeting to its final cellular compartment (25,(34)(35)(36).…”

mentioning

confidence: 99%

The Rhodobacter sphaeroides cytochrome c2 signal peptide is not necessary for export and heme attachment

Brandner

Donohue

1994

J Bacteriol

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“…In the experiment with added ions, the final concentrations of KCl and NaCl were 76 and 88 mM, respectively, due to the initial concentration of these ions in isolated lysates. Cytochrome c is synthesized on cytoplasmic ribosomes as the apo (non-heme-containing) form and transported into mitochondria, where heme is inserted to form holocytochrome c, which is retained in the intermembrane space (28). Since only holocytochrome c and not the apo form supports dATP-dependent activation of caspases in cell lysates (21,29), we analyzed control lysates with a holocytochrome c-specific antibody.…”

Section: Figmentioning

confidence: 99%

Physiological Concentrations of K+ Inhibit Cytochrome c-dependent Formation of the Apoptosome

Cain

Langlais²,

Sun

et al. 2001

Journal of Biological Chemistry

175

137

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In many forms of apoptosis, cytochrome c released from mitochondria induces the oligomerization of Apaf-1 to form a caspase-activating apoptosome complex. Activation of lysates in vitro with dATP and cytochrome c results in the formation of an active caspaseprocessing ϳ700-kDa apoptosome complex, which predominates in apoptotic cells, and a relatively inactive ϳ1.4-MDa complex. We now demonstrate that assembly of the active complex is suppressed by normal intracellular concentrations of K ؉ . Using a defined apoptosome reconstitution system with recombinant Apaf-1 and cytochrome c, K ؉ also inhibits caspase activation by abrogating Apaf-1 oligomerization and apoptosome assembly. Once assembled, the apoptosome is relatively insensitive to the effects of ionic strength and processes/ activates effector caspases. The inhibitory effects of K ؉ on apoptosome formation are antagonized in a concentrationdependent manner by cytochrome c. These studies support the hypothesis that the normal intracellular concentrations of K ؉ act to safeguard the cell against inappropriate formation of the apoptosome complex, caused by the inadvertent release of small amounts of cytochrome c. Thus, the assembly and activation of the apoptosome complex in the cell requires the rapid and extensive release of cytochrome c to overcome the inhibitory effects of normal intracellular concentrations of K ؉

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“…Proteins can be either stop-transfer-sorted or conservative-sorted, with the latter pathway using the Oxa1p translocase located on the inner mitochondrial membrane (10). A variety of other protein import pathways also exist, such as those utilized for the import of cytochrome c (11) and the small Tim proteins of the intermembrane space (12,13).…”

mentioning

confidence: 99%

Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes

Carrie

Giraud

Duncan

et al. 2010

Journal of Biological Chemistry

101

113

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The disulfide relay system of the mitochondrial intermembrane space has been extensively characterized in Saccharomyces cerevisiae. It contains two essential components, Mia40 and Erv1. The genome of Arabidopsis thaliana contains a single gene for each of these components. Although insertional inactivation of Erv1 leads to a lethal phenotype, inactivation of Mia40 results in no detectable deleterious phenotype. A. thaliana Mia40 is targeted to and accumulates in mitochondria and peroxisomes. Inactivation of Mia40 results in an alteration of several proteins in mitochondria, an absence of copper/zinc superoxide dismutase (CSD1), the chaperone for superoxide dismutase (Ccs1) that inserts copper into CSD1, and a decrease in capacity and amount of complex I. In peroxisomes the absence of Mia40 leads to an absence of CSD3 and a decrease in abnormal inflorescence meristem 1 (Aim1), a ␤-oxidation pathway enzyme. Inactivation of Mia40 leads to an alteration of the transcriptome of A. thaliana, with genes encoding peroxisomal proteins, redox functions, and biotic stress significantly changing in abundance. Thus, the mechanistic operation of the mitochondrial disulfide relay system is different in A. thaliana compared with other systems, and Mia40 has taken on new roles in peroxisomes and mitochondria.Characterization of the proteomes of mitochondria from Saccharomyces cerevisiae (yeast), mammals, and plants indicates that they contain from 1000 proteins in yeast to ϳ2000 in higher organisms (1). As the coding capacity of mitochondria is limited to between 8 and approximately 50 proteins in yeast and plants, respectively (2), the majority of mitochondrial proteins are encoded by nuclear located genes, translated in the cytosol, and imported into mitochondria. The import of hundreds of different proteins is achieved by the combined action of a number of multisubunit, integral membrane protein complexes, known as translocases. These translocases work in conjunction with a variety of soluble components located in the cytosol, intermembrane space, and mitochondrial matrix, such as chaperones, peptidases, and assembly factors (3, 4).The outer mitochondrial membrane contains the TOM complex (translocase of the outer membrane) and the sorting and assembly machinery; the latter is also known as the TOB complex (topogenesis of ␤-barrel proteins) (4). Almost all mitochondrial proteins are initially recognized by the outer membrane complex and are passed to other components depending on their final location. ␤-Barrel proteins of the outer membrane such as Tom40 and voltage-dependent anion channel protein (VDAC) are passed to the sorting and assembly machinery complex (5). Proteins imported via the general and carrier import pathways are passed to the translocases of the inner membrane 23 (TIM23) and 22 (TIM22), respectively (3, 4). Proteins are passed to the TIM23 complex directly from the outer membrane complex with the aid of Tim50 (6, 7) and also possibly Tim23, where the N-terminal region has been shown to transiently associate ...

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Apocytochrome c: an exceptional mitochondrial precursor protein using an exceptional import pathway

Cited by 83 publications

References 69 publications

The Rhodobacter sphaeroides cytochrome c2 signal peptide is not necessary for export and heme attachment

The Rhodobacter sphaeroides cytochrome c2 signal peptide is not necessary for export and heme attachment

Physiological Concentrations of K+ Inhibit Cytochrome c-dependent Formation of the Apoptosome

Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes

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