Porins in mitochondria

Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane TOM complex forms the main entry site for precursor proteins that are produced on cytosolic ribosomes, porins in mitochondria. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membranes, the intermembrane space, and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel VDAC porins in mitochondria, in mitochondrial protein biogenesis.

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Mitochondrial porins, or voltage-dependent anion-selective channels VDAC allow the passage of small molecules across the mitochondrial outer membrane, and are involved in complex interactions regulating organellar and cellular metabolism. Numerous organisms possess multiple porin isoforms, and initial studies indicated an intriguing evolutionary history for these proteins and the genes that encode them.

Porins in mitochondria

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Porin, also termed the voltage-dependent anion channel, is the most abundant protein of the mitochondrial outer membrane. The process of import and assembly of the protein is known to be dependent on the surface receptor Tom20, but the requirement for other mitochondrial proteins remains controversial. We have used mitochondria from Neurospora crassa and Saccharomyces cerevisiae to analyze the import pathway of porin. Import of porin into isolated mitochondria in which the outer membrane has been opened is inhibited despite similar levels of Tom20 as in intact mitochondria. A matrix-destined precursor and the porin precursor compete for the same translocation sites in both normal mitochondria and mitochondria whose surface receptors have been removed, suggesting that both precursors utilize the general import pore. Using an assay established to monitor the assembly of in vitro—imported porin into preexisting porin complexes we have shown that besides Tom20, the biogenesis of porin depends on the central receptor Tom22, as well as Tom5 and Tom7 of the general import pore complex translocase of the outer mitochondrial membrane [TOM] core complex. The characterization of two new mutant alleles of the essential pore protein Tom40 demonstrates that the import of porin also requires a functional Tom Moreover, the porin precursor can be cross-linked to Tom20, Tom22, and Tom40 on its import pathway. We conclude that import of porin does not proceed through the action of Tom20 alone, but requires an intact outer membrane and involves at least four more subunits of the TOM machinery, including the general import pore. Most mitochondrial precursor proteins are encoded by nuclear genes, synthesized on cytosolic ribosomes and imported into the organelle via the action of complexes comprised of multisubunit translocases in the outer TOM and the inner TIM mitochondrial membranes Neupert ; Pfanner et al. The surface receptors Tom70, Tom22, and Tom20 expose large domains to the cytosol.

Synthesis and radiolabeling of mitochondrial precursor proteins was performed with rabbit reticulocyte lysate Amersham Pharmacia Biotech or the TNT-coupled reticulocyte lysate system Promega Rassow

Porins are beta barrel proteins that cross a cellular membrane and act as a pore, through which molecules can diffuse. They are present in the outer membrane of gram-negative bacteria and some gram-positive mycobacteria mycolic acid-containing actinomycetes , the outer membrane of mitochondria , and the outer chloroplast membrane outer plastid membrane. This means that the nonpolar residues face outward so as to interact with the nonpolar lipids of outer membrane , whereas the polar residues face inwards into the center of the beta barrel to create the aqueous channel. The specific amino acids in the channel determine the specificity of the porin to different molecules. The individual strands are joined together by loops and turns. All porins form homotrimers in the outer membrane, meaning that three identical porin subunits associate together to form a porin super-structure with three channels.

Metrics details. Biological energy conversion in mitochondria is carried out by the membrane protein complexes of the respiratory chain and the mitochondrial ATP synthase in the inner membrane cristae. Recent advances in electron cryomicroscopy have made possible new insights into the structural and functional arrangement of these complexes in the membrane, and how they change with age. This review places these advances in the context of what is already known, and discusses the fundamental questions that remain open but can now be approached. Mitochondria are the powerhouses of the cell. In all eukaryotes that do not depend on photosynthesis, the mitochondria are the main source of adenosine triphosphate ATP , the energy-rich compound that drives fundamental cell functions.

Porins in mitochondria

Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane TOM complex forms the main entry site for precursor proteins that are produced on cytosolic ribosomes. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membranes, the intermembrane space, and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel VDAC , in mitochondrial protein biogenesis. Porin forms the major channel for metabolites and ions in the outer membrane of mitochondria. Two different functions of porin in protein translocation have been reported. First, it controls the formation of the TOM complex by modulating the integration of the central receptor Tom22 into the mature translocase. Second, porin promotes the transport of carrier proteins toward the carrier translocase TIM22 complex , which inserts these preproteins into the inner membrane. Therefore, porin acts as a coupling factor to spatially coordinate outer and inner membrane transport steps.

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Therefore, twelve representative animal, plant, and fungal VDAC genes including paralogs were examined for the number of introns present, intron phasing, and the position of introns with respect to functional and structural motifs Figs. With respect to gene duplication events, it appears that among the Saccharomycetales a lineage is present that displays the presence of paralogs node 10, Fig. Porins from mitochondrial and bacterial outer membranesstructural and functional aspects. The proteins have the same length but they exhibit some differences, in particular in the number of cysteines. Porin forms high molecular weight complexes in yeast. Purification and characterization of Porin from corn Zea mays L. Structure of the human voltage-dependent anion channel. Sections Sections. Peptide-specific antibodies as probes of the topography of the voltage-gated channel in the mitochondrial outer membrane of Neurospora crassa. Further evidence comes from cell lines and knock-out mice lacking porin isoforms singly or in combination [ 45 ]. Purification and characterization of the pore forming protein of yeast mitochondrial outer membrane. In analogy to their work with bacterial porins, they were able to reconstitute fragments of the mitochondrial outer membranes into vesicles from soybean lipids and demonstrated that the vesicles became permeable for low molecular mass carbohydrates but not for high molecular mass dextrans. Mitochondrion 19, — Journal of Bacteriology.

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Using a variety of different porin sequences as queries, GenBank was searched via blastp and tblastx against previously published VDAC sequences from related organisms. The open to closed ratio of the pores is given by the analysis of the experimental results of experiments similar to Figure 1 according to:. The pore had a conductance of 0. Interaction of mitochondrial porin with cytosolic proteins. Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability. Import pathways of precursor proteins into mitochondriamultiple receptor sites are followed by a common membrane insertion site. Evidence for identity between the hexokinase-binding protein and the mitochondrial porin in the outer membrane of rat liver mitochondria. To verify their results, they demonstrated that yeast porin was not accessible for protease treatment as long the protein was localized in the mitochondrial outer membrane Mihara et al. Figure 6. These specificities are determined by the threshold sizes of the porins, and the amino acid residues lining them. The VDAC amino acid sequences from members of the three crown groups formed monophyletic groupings and the branching patterns suggest that the animal and fungal porins are derived from a common ancestor. Both amino- and carboxy-terminal portions are required for insertion of yeast porin into the outer mitochondrial membrane. Figure 1. EMBO J. Grevel, A.