Successive translocation into and out of the mitochondrial matrix: Targeting of proteins to the intermembrane space by a bipartite signal peptide

Hartl, F. Ulrich; Ostermann, Joachim; Guiard, Bernard; Neupert, Walter

doi:10.1016/0092-8674(87)90589-7

Cited by 270 publications

(151 citation statements)

References 66 publications

(55 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…Similar results are obtained for the import of cytochrome b^ and cytochrome c.j (26). Cytochrome b^ is a soluble component of the intermembrane space while cytochrome is anchored to the inner membrane but faces the intermembrane space with a large hydrophilic domain.…”

Section: Import Intermediates In the Mitochondrial Matrixsupporting

confidence: 72%

Protein transport into mitochondria

Herrmann¹,

Neupert²

2000

Current Opinion in Microbiology

Self Cite

140

View full text Add to dashboard Cite

Section: Import Intermediates In the Mitochondrial Matrixsupporting

confidence: 72%

Protein transport into mitochondria

Herrmann¹,

Neupert²

2000

Current Opinion in Microbiology

Self Cite

140

View full text Add to dashboard Cite

“…The second part ('sorting sequence') directs the protein to the intermembrane space and resembles bacterial leader sequences. For the intramitochondrial sorting of these proteins two models are being discussed: (i) according to the 'conservative sorting' mechanism the protein is first imported into the matrix and then, in a second step, retranslocated across the inner membrane [49]; (ii) alternatively, the protein would become arrested in the inner membrane by the sorting sequence ('stoptransfer') and directly be released to the intermembrane space [50].…”

Section: Bioenergetics Of Mitochondrial Protein Import and Sortingmentioning

confidence: 99%

Mitochondrial protein import: Mechanisms, components and energetics

Schwarz

Neupert

1994

Biochimica et Biophysica Acta (BBA) - Bioenergetics

Self Cite

View full text Add to dashboard Cite

The transport of nuclear-encoded proteins from the cytosol into mitochondria is mediated by targeting (signal) sequences present on precursor forms. Most precursors of the mitochondrial matrix possess amino-terminal signals which characteristically contain hydroxylated and basic amino acids and lack acidic residues. With a minority of precursor proteins, internal sequence motifs can direct proteins to the mitochondria (Planner, N., Hoeben, P., Tropschug, M. and Neupert, W. (1987) J. Biol. Chem. 262, 14851-14854). The presence of a mitochondrial targeting sequence alone, however, is not sufficient for specific targeting to the organeUe and further to the various subcompartments. There is the need for components which recognise the targeting sequences and others which keep the precursor protein in a translocation-competent form. Beyond the recognition step, components are required which mediate transiocation across the mitochondrial membranes. Mitochondria possess two translocation machineries, one in the outer membrane and one in the inner membrane. The matrix space harbors a number of factors which participate in the import of proteins, in their unfolding and folding. Energy is required at several steps of these processes.

show abstract

“…There are several precedents for bipartite signaling peptides; ornithine transcarbamylase is imported into the mitochondria in a two-stage cleavage process [27]. In other mitochondrial proteins such as cytochrome b2 and cytochrome c1, bipartite signaling peptides containing a hydrophobic stretch are thought to be a suborganellar sorting signal [28,29]. Unlike the bipartite signal seen in the cytochrome proteins, the variable domain is not particularly hydrophobic, suggesting a different role for this region of NAGS.…”

Section: Post-translational Processingmentioning

confidence: 99%

Mammalian N-acetylglutamate synthase

Morizono

Caldovic

Shi

et al. 2004

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

N-Acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI). The mouse and human NAGS genes have been identified based on similarity to regions of NAGS from Neurospora crassa and cloned from liver cDNA libraries. These genes were shown to complement an argA-(NAGS) deficient Escherichia coli strain, and enzymatic activity of the proteins was confirmed by a new stable isotope dilution assay. The deduced amino acid sequence of mammalian NAGS contains a putative mitochondrial-targeting signal at the Nterminus. The mouse NAGS preprotein was overexpressed in insect cells to determine posttranslational modifications and two processed proteins with different N-terminal truncations have been identified. Sequence analysis using a hidden Markov model suggests that the vertebrate NAGS protein contains domains with a carbamate kinase fold and an acyl-CoA N-acyltransferase fold, and protein crystallization experiments are currently underway. Inherited NAGS deficiency results in hyperammonemia, presumably due to the loss of CPSI activity. We, and others, have recently identified mutations in families with neonatal and late-onset NAGS deficiency and the identification of the gene has now made carrier testing and prenatal diagnosis feasible. A structural analog of NAG, carbamylglutamate, has been shown to bind and activate CPSI, and several patients have been reported to respond favorably to this drug (Carbaglu®).

show abstract

Successive translocation into and out of the mitochondrial matrix: Targeting of proteins to the intermembrane space by a bipartite signal peptide

Cited by 270 publications

References 66 publications

Protein transport into mitochondria

Protein transport into mitochondria

Mitochondrial protein import: Mechanisms, components and energetics

Mammalian N-acetylglutamate synthase

Contact Info

Product

Resources

About