scholarly journals The SLC25 Carrier Family: Important Transport Proteins in Mitochondrial Physiology and Pathology

Physiology ◽  
2020 ◽  
Vol 35 (5) ◽  
pp. 302-327 ◽  
Author(s):  
Edmund R. S. Kunji ◽  
Martin S. King ◽  
Jonathan J. Ruprecht ◽  
Chancievan Thangaratnarajah
Keyword(s):  
Molecular Basis ◽  
Transport Mechanism ◽  
Building Blocks ◽  
Transport Proteins ◽  
Current Understanding ◽  
Mitochondrial Matrix ◽  
Inner Membrane ◽  
Mitochondrial Carrier ◽  
Mitochondrial Carrier Family

Members of the mitochondrial carrier family (SLC25) transport a variety of compounds across the inner membrane of mitochondria. These transport steps provide building blocks for the cell and link the pathways of the mitochondrial matrix and cytosol. An increasing number of diseases and pathologies has been associated with their dysfunction. In this review, the molecular basis of these diseases is explained based on our current understanding of their transport mechanism.

scholarly journals The Mimivirus Genome Encodes a Mitochondrial Carrier That Transports dATP and dTTP

2007 ◽  
Vol 81 (7) ◽  
pp. 3181-3186 ◽  
Author(s):  
Magnus Monné ◽  
Alan J. Robinson ◽  
Christoph Boes ◽  
Michael E. Harbour ◽  
Ian M. Fearnley ◽  
...  
Keyword(s):  
Lactococcus Lactis ◽  
Viral Protein ◽  
Metabolic Pathways ◽  
Transport Proteins ◽  
Inner Membrane ◽  
Mitochondrial Carrier ◽  
Mitochondrial Inner Membrane ◽  
Double Stranded Dna ◽  
The Matrix ◽  
Mitochondrial Carrier Family

ABSTRACT Members of the mitochondrial carrier family have been reported in eukaryotes only, where they transport metabolites and cofactors across the mitochondrial inner membrane to link the metabolic pathways of the cytosol and the matrix. The genome of the giant virus Mimiviridae mimivirus encodes a member of the mitochondrial carrier family of transport proteins. This viral protein has been expressed in Lactococcus lactis and is shown to transport dATP and dTTP. As the 1.2-Mb double-stranded DNA mimivirus genome is rich in A and T residues, we speculate that the virus is using this protein to target the host mitochondria as a source of deoxynucleotides for its replication.

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.

Characterization of lipopolysaccharide transport protein complex

2014 ◽  
Vol 9 (2) ◽  
pp. 131-138
Author(s):  
Quanju Xiang ◽  
Haiyan Wang ◽  
Zhongshan Wang ◽  
Yizheng Zhang ◽  
Changjiang Dong
Keyword(s):  
Transport Mechanism ◽  
Transport Proteins ◽  
Gram Negative Bacteria ◽  
Inner Membrane ◽  
Toxic Compounds ◽  
Outer Membranes ◽  
Harsh Conditions ◽  
Cytoplasmic Side

AbstractLipopolysaccharide (LPS) is an essential component of the outer membranes (OM) of most Gram-negative bacteria, which plays a crucial role in protection of the bacteria from toxic compounds and harsh conditions. The LPS is biosynthesized at the cytoplasmic side of inner membrane (IM), and then transported across the aqueous periplasmic compartment and assembled correctly at the outer membrane. This process is accomplished by seven LPS transport proteins (LptA-G), but the transport mechanism remains poorly understood. Here, we present findings by pull down assays in which the periplasmic component LptA interacts with both the IM complex LptBFGC and the OM complex LptDE in vitro, but not with complex LptBFG. Using purified Lpt proteins, we have successfully reconstituted the seven transport proteins as a complex in vitro. In addition, the LptC may play an essential role in regulating the conformation of LptBFG to secure the lipopolysaccharide from the inner membrane. Our results contribute to the understanding of lipopolysaccharide transport mechanism and will provide a platform to study the detailed mechanism of the LPS transport in vitro.

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 Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane

2008 ◽  
Vol 182 (5) ◽  
pp. 937-950 ◽  
Author(s):  
Steven M. Claypool ◽  
Yavuz Oktay ◽  
Pinmanee Boontheung ◽  
Joseph A. Loo ◽  
Carla M. Koehler
Keyword(s):  
Oxidative Phosphorylation ◽  
Respiratory Function ◽  
Protein Complexes ◽  
Progressive External Ophthalmoplegia ◽  
Carrier Protein ◽  
Affinity Tag ◽  
Inner Membrane ◽  
Mitochondrial Carrier ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Carrier Family

Defined mutations in the mitochondrial ADP/ATP carrier (AAC) are associated with certain types of progressive external ophthalmoplegia. AAC is required for oxidative phosphorylation (OXPHOS), and dysregulation of AAC has been implicated in apoptosis. Little is known about the AAC interactome, aside from a known requirement for the phospholipid cardiolipin (CL) and that it is thought to function as a homodimer. Using a newly developed dual affinity tag, we demonstrate that yeast AAC2 physically participates in several protein complexes of distinct size and composition. The respiratory supercomplex and several smaller AAC2-containing complexes, including other members of the mitochondrial carrier family, are identified here. In the absence of CL, most of the defined interactions are destabilized or undetectable. The absence of CL and/or AAC2 results in distinct yet additive alterations in respiratory supercomplex structure and respiratory function. Thus, a single lipid can significantly alter the functional interactome of an individual protein.

scholarly journals A Single Cysteine Residue in the Translocation Pathway of the Mitosomal ADP/ATP Carrier from Cryptosporidium parvum Confers a Broad Nucleotide Specificity

2020 ◽  
Vol 21 (23) ◽  
pp. 8971
Author(s):  
Martin S. King ◽  
Sotiria Tavoulari ◽  
Vasiliki Mavridou ◽  
Alannah C. King ◽  
John Mifsud ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Cysteine Residue ◽  
Transport Proteins ◽  
Serine Residue ◽  
Mitochondrial Carrier ◽  
Hydrophobic Residues ◽  
Mitochondrial Carrier Family ◽  
Mitochondrial Origin ◽  
Translocation Pathway ◽  
Nucleotide Specificity

Cryptosporidiumparvum is a clinically important eukaryotic parasite that causes the disease cryptosporidiosis, which manifests with gastroenteritis-like symptoms. The protist has mitosomes, which are organelles of mitochondrial origin that have only been partially characterized. The genome encodes a highly reduced set of transport proteins of the SLC25 mitochondrial carrier family of unknown function. Here, we have studied the transport properties of one member of the C. parvum carrier family, demonstrating that it resembles the mitochondrial ADP/ATP carrier of eukaryotes. However, this carrier has a broader substrate specificity for nucleotides, transporting adenosine, thymidine, and uridine di- and triphosphates in contrast to its mitochondrial orthologues, which have a strict substrate specificity for ADP and ATP. Inspection of the putative translocation pathway highlights a cysteine residue, which is a serine in mitochondrial ADP/ATP carriers. When the serine residue is replaced by cysteine or larger hydrophobic residues in the yeast mitochondrial ADP/ATP carrier, the substrate specificity becomes broad, showing that this residue is important for nucleotide base selectivity in ADP/ATP carriers.

scholarly journals Proteomic and Bioinformatic Profiling of Transporters in Higher Plant Mitochondria

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1190 ◽  
Author(s):  
Ian Max Møller ◽  
R. Shyama Prasad Rao ◽  
Yuexu Jiang ◽  
Jay J. Thelen ◽  
Dong Xu
Keyword(s):  
Plant Mitochondria ◽  
Inorganic Ions ◽  
Proteomic Profiling ◽  
Inner Mitochondrial Membrane ◽  
Higher Plant ◽  
Inner Membrane ◽  
Mitochondrial Carrier ◽  
Protein Uptake ◽  
Mitochondrial Carrier Family ◽  
Unexplored Area

To function as a metabolic hub, plant mitochondria have to exchange a wide variety of metabolic intermediates as well as inorganic ions with the cytosol. As identified by proteomic profiling or as predicted by MU-LOC, a newly developed bioinformatics tool, Arabidopsis thaliana mitochondria contain 128 or 143 different transporters, respectively. The largest group is the mitochondrial carrier family, which consists of symporters and antiporters catalyzing secondary active transport of organic acids, amino acids, and nucleotides across the inner mitochondrial membrane. An impressive 97% (58 out of 60) of all the known mitochondrial carrier family members in Arabidopsis have been experimentally identified in isolated mitochondria. In addition to many other secondary transporters, Arabidopsis mitochondria contain the ATP synthase transporters, the mitochondria protein translocase complexes (responsible for protein uptake across the outer and inner membrane), ATP-binding cassette (ABC) transporters, and a number of transporters and channels responsible for allowing water and inorganic ions to move across the inner membrane driven by their transmembrane electrochemical gradient. A few mitochondrial transporters are tissue-specific, development-specific, or stress-response specific, but this is a relatively unexplored area in proteomics that merits much more attention.

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