scholarly journals Functions of the Small Proteins in the TOM Complex of Neurospora crasssa

2005 ◽  
Vol 16 (9) ◽  
pp. 4172-4182 ◽  
Author(s):  
E. Laura Sherman ◽  
Nancy E. Go ◽  
Frank E. Nargang
Keyword(s):  
Mitochondrial Membrane ◽  
Minor Role ◽  
Complex Stability ◽  
Outer Mitochondrial Membrane ◽  
The Core ◽  
Tom Complex ◽  
Membrane Complex ◽  
Small Proteins ◽  
Precursor Proteins ◽  
A Minor

The TOM (translocase of the outer mitochondrial membrane) complex of the outer mitochondrial membrane is required for the import of proteins into the organelle. The core TOM complex contains five proteins, including three small components Tom7, Tom6, and Tom5. We have created single and double mutants of all combinations of the three small Tom proteins of Neurospora crassa. Analysis of the mutants revealed that Tom6 plays a major role in TOM complex stability, whereas Tom7 has a lesser role. Mutants lacking both Tom6 and Tom7 have an extremely labile TOM complex and are the only class of mutant to exhibit an altered growth phenotype. Although single mutants lacking N. crassa Tom5 have no apparent TOM complex abnormalities, studies of double mutants lacking Tom5 suggest that it also has a minor role in maintaining TOM complex stability. Our inability to isolate triple mutants supports the idea that the three proteins have overlapping functions. Mitochondria lacking either Tom6 or Tom7 are differentially affected in their ability to import different precursor proteins into the organelle, suggesting that they may play roles in the sorting of proteins to different mitochondrial subcompartments. Newly imported Tom40 was readily assembled into the TOM complex in mitochondria lacking any of the small Tom proteins.

scholarly journals A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria

2014 ◽  
Vol 25 (25) ◽  
pp. 3999-4009 ◽  
Author(s):  
Agnieszka Gornicka ◽  
Piotr Bragoszewski ◽  
Piotr Chroscicki ◽  
Lena-Sophie Wenz ◽  
Christian Schulz ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Membrane ◽  
Alternative Pathway ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Membrane Translocation ◽  
Tom Complex ◽  
Precursor Proteins ◽  
Core Components

Mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria with the help of protein translocases. For the majority of precursor proteins, the role of the translocase of the outer membrane (TOM) and mechanisms of their transport across the outer mitochondrial membrane are well recognized. However, little is known about the mode of membrane translocation for proteins that are targeted to the intermembrane space via the redox-driven mitochondrial intermembrane space import and assembly (MIA) pathway. On the basis of the results obtained from an in organello competition import assay, we hypothesized that MIA-dependent precursor proteins use an alternative pathway to cross the outer mitochondrial membrane. Here we demonstrate that this alternative pathway involves the protein channel formed by Tom40. We sought a translocation intermediate by expressing tagged versions of MIA-dependent proteins in vivo. We identified a transient interaction between our model substrates and Tom40. Of interest, outer membrane translocation did not directly involve other core components of the TOM complex, including Tom22. Thus MIA-dependent proteins take another route across the outer mitochondrial membrane that involves Tom40 in a form that is different from the canonical TOM complex.

scholarly journals Mitochondrial Protein Import

2004 ◽  
Vol 279 (44) ◽  
pp. 45701-45707 ◽  
Author(s):  
Masatoshi Esaki ◽  
Hidaka Shimizu ◽  
Tomoko Ono ◽  
Hayashi Yamamoto ◽  
Takashi Kanamori ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Protein Import ◽  
Tom Complex ◽  
Membrane Complex ◽  
Cytosolic Side

Protein translocation across the outer mitochondrial membrane is mediated by the translocator called the TOM (translocase of the outer mitochondrial membrane) complex. The TOM complex possesses two presequence binding sites on the cytosolic side (thecissite) and on the intermembrane space side (thetranssite). Here we analyzed the requirement of presequence elements and subunits of the TOM complex for presequence binding to thecisandtranssites of the TOM complex. The N-terminal 14 residues of the presequence of subunit 9 of F0-ATPase are required for binding to thetranssite. The interaction between the presequence and thecissite is not sufficient to anchor the precursor protein to the TOM complex. Tom7 constitutes or is close to thetranssite and has overlapping functions with the C-terminal intermembrane space domain of Tom22 in the mitochondrial protein import.

scholarly journals How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane?

2005 ◽  
Vol 171 (3) ◽  
pp. 419-423 ◽  
Author(s):  
Doron Rapaport
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Mitochondrial Membrane ◽  
Mitochondrial Outer Membrane ◽  
Outer Face ◽  
Outer Mitochondrial Membrane ◽  
Lipid Core ◽  
Tom Complex ◽  
Precursor Proteins

A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane. The proposed β-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted β-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer. In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit β-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 β-barrel structure.

scholarly journals Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex

2021 ◽  
Author(s):  
Shafqat Rasool ◽  
Simon Veyron ◽  
Naoto Soya ◽  
Mohamed Eldeeb ◽  
Gergely Lukacs ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Mitochondrial Membrane ◽  
Autosomal Recessive ◽  
Kinase Activity ◽  
Mitochondrial Damage ◽  
Outer Mitochondrial Membrane ◽  
Dimer Interface ◽  
The Core ◽  
Tom Complex ◽  
Cytosolic Domain

Mutations in PINK1 causes autosomal-recessive Parkinson's disease. Mitochondrial damage results in PINK1 import arrest on the Translocase of the Outer Mitochondrial Membrane (TOM) complex, resulting in the activation of its ubiquitin kinase activity by autophosphorylation and initiation of Parkin-dependent mitochondrial clearance. Herein we report crystal structures of the entire cytosolic domain of insect PINK1. Our structures reveal a dimeric autophosphorylation complex targeting phosphorylation at the invariant Ser205 (human Ser228). The dimer interface requires insert 2, which is unique to PINK1. The structures also reveal how an N-terminal helix binds to the C-terminal extension and provide insights into stabilization of PINK1 on the core TOM complex.

scholarly journals Accuracy in Online Media

2020 ◽  
Vol 11 (21) ◽  
pp. 66-86
Author(s):  
Sandra Buratović Maštrapa ◽  
Romana John ◽  
Mato Brautović
Keyword(s):  
Error Correction ◽  
Online Media ◽  
Minor Role ◽  
Online Environment ◽  
Secondary Sources ◽  
The Core ◽  
Propagation Of Errors ◽  
A Minor ◽  
Error Correction Procedures ◽  
Visual Network

Accuracy is at the core of what journalists do and it amounts to journalistic commitment to report without errors. This tenet of journalism is now in danger, because of the influence of digitalization, changes in media landscapes, and the utilization of the assertation model of journalism. In this study, we used a combination of content analysis and visual network analysis to investigate how subjective errors are disseminated through an online environment, how time/speed influences the propagation of errors, and what the error correction procedures/routines are. The results demonstrate that 69% of the analyzed stories contained errors, and the main cause of such errors was the use of secondary sources, instead of primary ones, these errors transcend national borders and, time/speed had only a minor role in the emergence and correction of the errors, etc. Out of the 107 media websites analyzed, only seventeen provide certain modalities of requesting error correction.

scholarly journals A novel USP30 inhibitor recapitulates genetic loss of USP30 and sets the trigger for PINK1-PARKIN amplification of mitochondrial ubiquitylation

2020 ◽  
Author(s):  
Emma Rusilowicz-Jones ◽  
Jane Jardine ◽  
Andreas Kallinos ◽  
Adan Pinto-Fernandez ◽  
Franziska Guenther ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Neuroblastoma Cell ◽  
Selective Inhibition ◽  
Neuroblastoma Cell Line ◽  
Outer Mitochondrial Membrane ◽  
Loss Of Function ◽  
Mitochondrial Mass ◽  
Tom Complex ◽  
Membrane Depolarisation ◽  
Disease Associated Genes

AbstractThe mitochondrial deubiquitylase USP30 negatively regulates the selective autophagy of damaged mitochondria. It has been proposed as an actionable target to alleviate the loss of function of the mitophagy pathway governed by the Parkinson’s Disease associated genes PINK1 and PRKN. We present the characterisation of a N-cyano pyrrolidine derived compound, FT3967385, with high selectivity for USP30. The compound is well tolerated with no loss of total mitochondrial mass. We demonstrate that ubiquitylation of TOM20, a component of the outer mitochondrial membrane import machinery that directly interacts with USP30, represents a robust biomarker for both USP30 loss and inhibition. We have conducted proteomics analyses on a SHSY5Y neuroblastoma cell line model to directly compare the effects of genetic loss of USP30 with selective inhibition in an unbiased fashion. We have thereby identified a subset of ubiquitylation events consequent to mitochondrial depolarisation that are USP30 sensitive. Within responsive elements of the ubiquitylome, several components of the outer mitochondrial membrane transport (TOM) complex are most prominent. Thus, our data support a model whereby USP30 can regulate the availability of ubiquitin at the specific site of mitochondrial PINK1 accumulation following membrane depolarisation. In this model, USP30 deubiquitylation of TOM complex components dampens the trigger for the Parkin-dependent amplification of mitochondrial ubiquitylation leading to mitophagy. Accordingly, PINK1 generation of phospho-Ser65 Ubiquitin proceeds more rapidly and to a greater extent in cells either lacking USP30 or subject to USP30 inhibition.

scholarly journals A Biochemical and Structural Understanding of TOM Complex Interactions and Implications for Human Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1164
Author(s):  
Ashley S. Pitt ◽  
Susan K. Buchanan
Keyword(s):  
Human Health ◽  
Mitochondrial Membrane ◽  
Cancer Metabolism ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Outer Mitochondrial Membrane ◽  
Tom Complex ◽  
Complex Interactions ◽  
Health And Disease ◽  
Function Relationship

The central role mitochondria play in cellular homeostasis has made its study critical to our understanding of various aspects of human health and disease. Mitochondria rely on the translocase of the outer membrane (TOM) complex for the bulk of mitochondrial protein import. In addition to its role as the major entry point for mitochondrial proteins, the TOM complex serves as an entry pathway for viral proteins. TOM complex subunits also participate in a host of interactions that have been studied extensively for their function in neurodegenerative diseases, cardiovascular diseases, innate immunity, cancer, metabolism, mitophagy and autophagy. Recent advances in our structural understanding of the TOM complex and the protein import machinery of the outer mitochondrial membrane have made structure-based therapeutics targeting outer mitochondrial membrane proteins during mitochondrial dysfunction an exciting prospect. Here, we describe advances in understanding the TOM complex, the interactome of the TOM complex subunits, the implications for the development of therapeutics, and our understanding of the structure/function relationship between components of the TOM complex and mitochondrial homeostasis.

Wild-type and mutant (G2019S) leucine-rich repeat kinase 2 (LRRK2) associate with subunits of the translocase of outer mitochondrial membrane (TOM) complex

2019 ◽  
Vol 375 (2) ◽  
pp. 72-79 ◽  
Author(s):  
Annika Neethling ◽  
Lize Engelbrecht ◽  
Ben Loos ◽  
Craig Kinnear ◽  
Rensu Theart ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Leucine Rich Repeat ◽  
Wild Type ◽  
Tom Complex

Electrostatic and nonelectrostatic, conventional and unitary thermodynamic quantities of reaction. II. Proton–ligand and metal–ligand reactions in mixed solvents

1986 ◽  
Vol 64 (4) ◽  
pp. 785-789 ◽  
Author(s):  
Roberto Aruga
Keyword(s):  
Dielectric Constant ◽  
Mixed Solvents ◽  
Minor Role ◽  
Thermodynamic Quantities ◽  
Complex Stability ◽  
Present Treatment ◽  
Leading Role ◽  
A Minor ◽  
Metal Ligand

A calculation method of the electrostatic and the nonelectrostatic parts of thermodynamic quantities of reaction, previously proposed and applied to association reactions in aqueous medium, is applied, in the present work, to reactions in mixed solvents. The aim of the present treatment is to clarify the importance of the various factors (dependent and independent of the dielectric constant) through which the solvent affects complex stability. The method is applied to ΔG0, ΔH0, and ΔS0 data of literature for proton–ligand and metal–ligand reactions in several water–methanol, water–ethanol, and water–dioxane mixtures. The conclusions of the present study seem to confirm a leading role of solvation equilibria in determining different stabilities of complex in different solvents, while a minor role is assigned to the dielectric properties of the solvent.

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