scholarly journals Mutations in a 19-amino-acid hydrophobic region of the yeast cytochrome c1 presequence prevent sorting to the mitochondrial intermembrane space.

1992 ◽  
Vol 12 (10) ◽  
pp. 4677-4686 ◽  
Author(s):  
R E Jensen ◽  
S Schmidt ◽  
R J Mark
Keyword(s):  
Amino Acid ◽  
Intermediate Form ◽  
Intermembrane Space ◽  
Protein Amino Acid ◽  
Hydrophobic Region ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cytochrome C1 ◽  
The Matrix ◽  
Hydrophobic Amino Acids ◽  
Mitochondrial Intermembrane Space

Most mitochondrial proteins destined for the intermembrane space (IMS) carry in their presequence information for localization to the IMS in addition to information for their import. By selecting for mutants in the yeast Saccharomyces cerevisiae that mislocalize an IMS-targeted fusion protein, we identified mutations in the IMS sorting signal of the cytochrome c1 protein. Amino acid substitutions or deletions in a stretch of 19 hydrophobic amino acids of the cytochrome c1 presequence resulted in accumulation of the intermediate form of the cytochrome c1 protein in the matrix. In some cases, the accumulated intermediate appeared to be slowly exported from the matrix, across the inner membrane to the IMS. Our results support the hypothesis that the cytochrome c1 precursor is normally imported completely into the matrix and then exported to the IMS.

Mutations in a 19-amino-acid hydrophobic region of the yeast cytochrome c1 presequence prevent sorting to the mitochondrial intermembrane space

1992 ◽  
Vol 12 (10) ◽  
pp. 4677-4686
Author(s):  
R E Jensen ◽  
S Schmidt ◽  
R J Mark
Keyword(s):  
Amino Acid ◽  
Intermediate Form ◽  
Intermembrane Space ◽  
Protein Amino Acid ◽  
Hydrophobic Region ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cytochrome C1 ◽  
The Matrix ◽  
Hydrophobic Amino Acids ◽  
Mitochondrial Intermembrane Space

Most mitochondrial proteins destined for the intermembrane space (IMS) carry in their presequence information for localization to the IMS in addition to information for their import. By selecting for mutants in the yeast Saccharomyces cerevisiae that mislocalize an IMS-targeted fusion protein, we identified mutations in the IMS sorting signal of the cytochrome c1 protein. Amino acid substitutions or deletions in a stretch of 19 hydrophobic amino acids of the cytochrome c1 presequence resulted in accumulation of the intermediate form of the cytochrome c1 protein in the matrix. In some cases, the accumulated intermediate appeared to be slowly exported from the matrix, across the inner membrane to the IMS. Our results support the hypothesis that the cytochrome c1 precursor is normally imported completely into the matrix and then exported to the IMS.

Computational studies of the mitochondrial carrier family SLC25. Present status and future perspectives

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrea Pasquadibisceglie ◽  
Fabio Polticelli
Keyword(s):  
Transport Mechanism ◽  
Experimental Studies ◽  
Intermembrane Space ◽  
Mitochondrial Carrier ◽  
Mitochondrial Homeostasis ◽  
The Matrix ◽  
Mitochondrial Carrier Family ◽  
Mitochondrial Intermembrane Space ◽  
Computational Analyses

Abstract The members of the mitochondrial carrier family, also known as solute carrier family 25 (SLC25), are transmembrane proteins involved in the translocation of a plethora of small molecules between the mitochondrial intermembrane space and the matrix. These transporters are characterized by three homologous domains structure and a transport mechanism that involves the transition between different conformations. Mutations in regions critical for these transporters’ function often cause several diseases, given the crucial role of these proteins in the mitochondrial homeostasis. Experimental studies can be problematic in the case of membrane proteins, in particular concerning the characterization of the structure–function relationships. For this reason, computational methods are often applied in order to develop new hypotheses or to support/explain experimental evidence. Here the computational analyses carried out on the SLC25 members are reviewed, describing the main techniques used and the outcome in terms of improved knowledge of the transport mechanism. Potential future applications on this protein family of more recent and advanced in silico methods are also suggested.

scholarly journals Compartmentation of cellular activities

2007 ◽  
Vol 28 (2) ◽  
pp. 64
Author(s):  
Trevor Lithgow
Keyword(s):  
Protein Transport ◽  
Yeast Cells ◽  
Yeast Genome ◽  
Intermembrane Space ◽  
Yeast Saccharomyces Cerevisiae ◽  
Technological Advances ◽  
The Matrix ◽  
Cellular Compartments ◽  
New Applications ◽  
Yeast Mutants

In the yeast Saccharomyces cerevisiae, almost one third of cellular function is concerned with maintaining the compartmentation of cellular activities. From classic studies in yeast genetics we have come to understand a great deal of the processes driving the delivery of proteins into these compartments and the metabolic advantages that this provides. With the publication of the yeast genome sequence, ?-omics? level studies began to provide further detail on the compartmentation of yeast cells. Very recent technological advances, including new applications in mass spectrometry, NMR, cryo-electron microscopy and the use of live-cell imaging have also been applied to yeast, because of the comparative analyses that can be done on yeast mutants. The mitochondrion is a complex compartment, carrying more than a thousand proteins that must be transported into and then distributed between, four sub-mitochondrial compartments. Essential molecular machinery in the outer and inner membranes, the intermembrane space and the matrix of mitochondria, drive protein transport, sorting and assembly. A glimpse of how S. cerevisiae and other microbes have provided understanding of cellular compartments is the aim of this review.

scholarly journals The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Heike Rampelt ◽  
Iva Sucec ◽  
Beate Bersch ◽  
Patrick Horten ◽  
Inge Perschil ◽  
...  
Keyword(s):  
Intermembrane Space ◽  
Inner Mitochondrial Membrane ◽  
Inner Membrane ◽  
Mitochondrial Carrier ◽  
Transmembrane Segments ◽  
Mitochondrial Inner Membrane ◽  
N Terminus ◽  
The Matrix ◽  
Mitochondrial Carrier Family ◽  
Mitochondrial Intermembrane Space

Abstract Background The mitochondrial pyruvate carrier (MPC) plays a central role in energy metabolism by transporting pyruvate across the inner mitochondrial membrane. Its heterodimeric composition and homology to SWEET and semiSWEET transporters set the MPC apart from the canonical mitochondrial carrier family (named MCF or SLC25). The import of the canonical carriers is mediated by the carrier translocase of the inner membrane (TIM22) pathway and is dependent on their structure, which features an even number of transmembrane segments and both termini in the intermembrane space. The import pathway of MPC proteins has not been elucidated. The odd number of transmembrane segments and positioning of the N-terminus in the matrix argues against an import via the TIM22 carrier pathway but favors an import via the flexible presequence pathway. Results Here, we systematically analyzed the import pathways of Mpc2 and Mpc3 and report that, contrary to an expected import via the flexible presequence pathway, yeast MPC proteins with an odd number of transmembrane segments and matrix-exposed N-terminus are imported by the carrier pathway, using the receptor Tom70, small TIM chaperones, and the TIM22 complex. The TIM9·10 complex chaperones MPC proteins through the mitochondrial intermembrane space using conserved hydrophobic motifs that are also required for the interaction with canonical carrier proteins. Conclusions The carrier pathway can import paired and non-paired transmembrane helices and translocate N-termini to either side of the mitochondrial inner membrane, revealing an unexpected versatility of the mitochondrial import pathway for non-cleavable inner membrane proteins.

scholarly journals A New Function in Translocation for the Mitochondrial i-AAA Protease Yme1: Import of Polynucleotide Phosphorylase into the Intermembrane Space

2006 ◽  
Vol 26 (22) ◽  
pp. 8488-8497 ◽  
Author(s):  
Robert N. Rainey ◽  
Jenny D. Glavin ◽  
Hsiao-Wen Chen ◽  
Samuel W. French ◽  
Michael A. Teitell ◽  
...  
Keyword(s):  
Protein Translocation ◽  
Rna Degradation ◽  
Mechanistic Study ◽  
Intermembrane Space ◽  
Polynucleotide Phosphorylase ◽  
Cellular Effects ◽  
The Matrix ◽  
Mitochondrial Intermembrane Space ◽  
Processing Peptidase

ABSTRACT Polynucleotide phosphorylase (PNPase) is an exoribonuclease and poly(A) polymerase postulated to function in the cytosol and mitochondrial matrix. Prior overexpression studies resulted in PNPase localization to both the cytosol and mitochondria, concurrent with cytosolic RNA degradation and pleiotropic cellular effects, including growth inhibition and apoptosis, that may not reflect a physiologic role for endogenous PNPase. We therefore conducted a mechanistic study of PNPase biogenesis in the mitochondrion. Interestingly, PNPase is localized to the intermembrane space by a novel import pathway. PNPase has a typical N-terminal targeting sequence that is cleaved by the matrix processing peptidase when PNPase engaged the TIM23 translocon at the inner membrane. The i-AAA protease Yme1 mediated translocation of PNPase into the intermembrane space but did not degrade PNPase. In a yeast strain deleted for Yme1 and expressing PNPase, nonimported PNPase accumulated in the cytosol, confirming an in vivo role for Yme1 in PNPase maturation. PNPase localization to the mitochondrial intermembrane space suggests a unique role distinct from its highly conserved function in RNA processing in chloroplasts and bacteria. Furthermore, Yme1 has a new function in protein translocation, indicating that the intermembrane space harbors diverse pathways for protein translocation.

scholarly journals The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways

Open Biology ◽  
2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Ruairidh Edwards ◽  
Ross Eaglesfield ◽  
Kostas Tokatlidis
Keyword(s):  
Protein Import ◽  
Atp Hydrolysis ◽  
Current Knowledge ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Mitochondrial Proteome ◽  
Normal Site ◽  
The Matrix ◽  
Human Disorders ◽  
Mitochondrial Intermembrane Space

The mitochondrial intermembrane space (IMS) is the most constricted sub-mitochondrial compartment, housing only about 5% of the mitochondrial proteome, and yet is endowed with the largest variability of protein import mechanisms. In this review, we summarize our current knowledge of the major IMS import pathway based on the oxidative protein folding pathway and discuss the stunning variability of other IMS protein import pathways. As IMS-localized proteins only have to cross the outer mitochondrial membrane, they do not require energy sources like ATP hydrolysis in the mitochondrial matrix or the inner membrane electrochemical potential which are critical for import into the matrix or insertion into the inner membrane. We also explore several atypical IMS import pathways that are still not very well understood and are guided by poorly defined or completely unknown targeting peptides. Importantly, many of the IMS proteins are linked to several human diseases, and it is therefore crucial to understand how they reach their normal site of function in the IMS. In the final part of this review, we discuss current understanding of how such IMS protein underpin a large spectrum of human disorders.

scholarly journals Analysis of the sorting signals directing NADH-cytochrome b5 reductase to two locations within yeast mitochondria.

1997 ◽  
Vol 17 (7) ◽  
pp. 4024-4032 ◽  
Author(s):  
V Haucke ◽  
C S Ocana ◽  
A Hönlinger ◽  
K Tokatlidis ◽  
N Pfanner ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Cytochrome B5 ◽  
Nuclear Gene ◽  
Intermembrane Space ◽  
Hydrophobic Region ◽  
Cytochrome B5 Reductase ◽  
Amino Terminal ◽  
Sorting Signals ◽  
The Matrix ◽  
Nadh Cytochrome

Mitochondrial NADH-cytochrome b5 reductase (Mcr1p) is encoded by a single nuclear gene and imported into two different submitochondrial compartments: the outer membrane and the intermembrane space. We now show that the amino-terminal 47 amino acids suffice to target the Mcr1 protein to both destinations. The first 12 residues of this sequence function as a weak matrix-targeting signal; the remaining residues are mostly hydrophobic and serve as an intramitochondrial sorting signal for the outer membrane and the intermembrane space. A double point mutation within the hydrophobic region of the targeting sequence virtually abolishes the ability of the precursor to be inserted into the outer membrane but increases the efficiency of transport into the intermembrane space. Import of Mcr1p into the intermembrane space requires an electrochemical potential across the inner membrane, as well as ATP in the matrix, and is strongly impaired in mitochondria lacking Tom7p or Tim11p, two components of the translocation machineries in the outer and inner mitochondrial membranes, respectively. These results indicate that intramitochondrial sorting of the Mcr1 protein is mediated by specific interactions between the bipartite targeting sequence and components of both mitochondrial translocation systems.

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