scholarly journals Protein import in mitochondria biogenesis: guided by targeting signals and sustained by dedicated chaperones

RSC Advances ◽  
2021 ◽  
Vol 11 (51) ◽  
pp. 32476-32493
Author(s):  
Anna-Roza Dimogkioka ◽  
Jamie Lees ◽  
Erik Lacko ◽  
Kostas Tokatlidis
Keyword(s):  
Amino Acids ◽  
Protein Import ◽  
Cellular Metabolism ◽  
Targeting Signals ◽  
Mitochondria Biogenesis

Mitochondria have a central role in cellular metabolism; they are responsible for the biosynthesis of amino acids, lipids, iron–sulphur clusters and regulate apoptosis.

scholarly journals TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import

2017 ◽  
Vol 216 (9) ◽  
pp. 2843-2858 ◽  
Author(s):  
Wei Wang ◽  
Zhi-Jie Xia ◽  
Jean-Claude Farré ◽  
Suresh Subramani
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Matrix Protein ◽  
Protein Import ◽  
Gene Mutations ◽  
Mulibrey Nanism ◽  
Peroxisomal Biogenesis ◽  
Peroxisomal Targeting ◽  
Targeting Signals ◽  
Peroxisomal Biogenesis Disorders

Most proteins destined for the peroxisomal matrix depend on the peroxisomal targeting signals (PTSs), which require the PTS receptor PEX5, whose deficiency causes fatal human peroxisomal biogenesis disorders (PBDs). TRIM37 gene mutations cause muscle–liver–brain–eye (mulibrey) nanism. We found that TRIM37 localizes in peroxisomal membranes and ubiquitylates PEX5 at K464 by interacting with its C-terminal 51 amino acids (CT51), which is required for PTS protein import. PEX5 mutations (K464A or ΔCT51), or TRIM37 depletion or mutation, reduce PEX5 abundance by promoting its proteasomal degradation, thereby impairing its functions in cargo binding and PTS protein import in human cells. TRIM37 or PEX5 depletion induces apoptosis and enhances sensitivity to oxidative stress, underscoring the cellular requirement for functional peroxisomes. Therefore, TRIM37-mediated ubiquitylation stabilizes PEX5 and promotes peroxisomal matrix protein import, suggesting that mulibrey nanism is a new PBD.

scholarly journals Protein Import into Hydrogenosomes of Trichomonas vaginalis Involves both N-Terminal and Internal Targeting Signals: a Case Study of Thioredoxin Reductases

2008 ◽  
Vol 7 (10) ◽  
pp. 1750-1757 ◽  
Author(s):  
Marek Mentel ◽  
Verena Zimorski ◽  
Patrick Haferkamp ◽  
William Martin ◽  
Katrin Henze
Keyword(s):  
Trichomonas Vaginalis ◽  
Protein Import ◽  
Atp Synthesis ◽  
Antioxidant Systems ◽  
Low Oxygen ◽  
Oxygen Sensitive ◽  
Targeting Signal ◽  
Targeting Signals ◽  
Thioredoxin Reductases

ABSTRACT The parabasalian flagellate Trichomonas vaginalis harbors mitochondrion-related and H2-producing organelles of anaerobic ATP synthesis, called hydrogenosomes, which harbor oxygen-sensitive enzymes essential to its pyruvate metabolism. In the human urogenital tract, however, T. vaginalis is regularly exposed to low oxygen concentrations and therefore must possess antioxidant systems protecting the organellar environment against the detrimental effects of molecular oxygen and reactive oxygen species. We have identified two closely related hydrogenosomal thioredoxin reductases (TrxRs), the hitherto-missing component of a thioredoxin-linked hydrogenosomal antioxidant system. One of the two hydrogenosomal TrxR isoforms, TrxRh1, carried an N-terminal extension resembling known hydrogenosomal targeting signals. Expression of hemagglutinin-tagged TrxRh1 in transfected T. vaginalis cells revealed that its N-terminal extension was necessary to import the protein into the organelles. The second hydrogenosomal TrxR isoform, TrxRh2, had no N-terminal targeting signal but was nonetheless efficiently targeted to hydrogenosomes. N-terminal presequences from hydrogenosomal proteins with known processing sites, i.e., the alpha subunit of succinyl coenzyme A synthetase (SCSα) and pyruvate:ferredoxin oxidoreductase A, were investigated for their ability to direct mature TrxRh1 to hydrogenosomes. Neither presequence directed TrxRh1 to hydrogenosomes, indicating that neither extension is, by itself, sufficient for hydrogenosomal targeting. Moreover, SCSα lacking its N-terminal extension was efficiently imported into hydrogenosomes, indicating that this extension is not required for import of this major hydrogenosomal protein. The finding that some hydrogenosomal enzymes require N-terminal signals for import but that in others the N-terminal extension is not necessary for targeting indicates the presence of additional targeting signals within the mature subunits of several hydrogenosome-localized proteins.

Mechanism of protein import across the chloroplast envelope

2000 ◽  
Vol 28 (4) ◽  
pp. 485-491 ◽  
Author(s):  
K. Chen ◽  
X. Chen ◽  
D. J. Schnell
Keyword(s):  
Protein Import ◽  
Essential Elements ◽  
Chloroplast Envelope ◽  
Envelope Membrane ◽  
Outer Envelope ◽  
Double Membrane ◽  
Protein Subunits ◽  
Targeting Signals ◽  
Outer Envelope Membrane ◽  
Envelope Membranes

The development and maintenance of chloroplasts relies on the contribution of protein subunits from both plastid and nuclear genomes. Most chloroplast proteins are encoded by nuclear genes and are post-translationally imported into the organelle across the double membrane of the chloroplast envelope. Protein import into the chloroplast consists of two essential elements: the specific recognition of the targeting signals (transit sequences) of cytoplasmic preproteins by receptors at the outer envelope membrane and the subsequent translocation of preproteins simultaneously across the double membrane of the envelope. These processes are mediated via the co-ordinate action of protein translocon complexes in the outer (Toe apparatus) and inner (Tic apparatus) envelope membranes.

Protein import into orangelles: Hierarchical targeting signals

Cell ◽  
1986 ◽  
Vol 46 (3) ◽  
pp. 321-322 ◽  
Author(s):  
Alan Colman ◽  
Colin Robinson
Keyword(s):  
Protein Import ◽  
Targeting Signals

Plant mitochondrial protein import: mechanisms and control

1999 ◽  
Vol 26 (8) ◽  
pp. 725 ◽  
Author(s):  
James Whelan
Keyword(s):  
Protein Import ◽  
Current Knowledge ◽  
Mitochondrial Protein ◽  
Mitochondrial Proteins ◽  
Mitochondrial Protein Import ◽  
Future Directions ◽  
Receptor Structure ◽  
Processing Peptidase ◽  
Targeting Signals ◽  
And Control

The characterisation of components of the plant mitochondrial import apparatus along with the availability of over one hundred nuclear-encoded mitochondrial proteins allows the study of plant mitochondrial protein import in homologous systems. From these studies it has emerged that although similarities in the import process exist with other organisms, significance differences exist, such as receptor structure, location of processing peptidase and targeting signals. These differences mean that previous studies carried out in heterologous systems must be re-evaluated. Further studies into protein import in plants need to be directed at understanding the mechanism of import and how this process may be controlled. In this review the latter points will be dealt with in terms of summarising our current knowledge and possible future directions.

scholarly journals The unique degradation pathway of the PTS2 receptor, Pex7, is dependent on the PTS receptor/coreceptor, Pex5 and Pex20

2014 ◽  
Vol 25 (17) ◽  
pp. 2634-2643 ◽  
Author(s):  
Danielle Hagstrom ◽  
Changle Ma ◽  
Soumi Guha-Polley ◽  
Suresh Subramani
Keyword(s):  
Matrix Protein ◽  
Protein Import ◽  
Degradation Pathway ◽  
Matrix Proteins ◽  
Receptor Recycling ◽  
Wild Type ◽  
The Matrix ◽  
Peroxisomal Targeting ◽  
Targeting Signals ◽  
The Stability

Peroxisomal matrix protein import uses two peroxisomal targeting signals (PTSs). Most matrix proteins use the PTS1 pathway and its cargo receptor, Pex5. The PTS2 pathway is dependent on another receptor, Pex7, and its coreceptor, Pex20. We found that during the matrix protein import cycle, the stability and dynamics of Pex7 differ from those of Pex5 and Pex20. In Pichia pastoris, unlike Pex5 and Pex20, Pex7 is constitutively degraded in wild-type cells but is stabilized in pex mutants affecting matrix protein import. Degradation of Pex7 is more prevalent in cells grown in methanol, in which the PTS2 pathway is nonessential, in comparison with oleate, suggesting regulation of Pex7 turnover. Pex7 must shuttle into and out of peroxisomes before it is polyubiquitinated and degraded by the proteasome. The shuttling of Pex7, and consequently its degradation, is dependent on the receptor recycling pathways of Pex5 and Pex20 and relies on an interaction between Pex7 and Pex20. We also found that blocking the export of Pex20 from peroxisomes inhibits PTS1-mediated import, suggesting sharing of limited components in the export of PTS receptors/coreceptors. The shuttling and stability of Pex7 are divergent from those of Pex5 and Pex20, exemplifying a novel interdependence of the PTS1 and PTS2 pathways.

scholarly journals Interdependence of the Peroxisome-targeting Receptors in Arabidopsis thaliana: PEX7 Facilitates PEX5 Accumulation and Import of PTS1 Cargo into Peroxisomes

2010 ◽  
Vol 21 (7) ◽  
pp. 1263-1271 ◽  
Author(s):  
Naxhiely Martínez Ramón ◽  
Bonnie Bartel
Keyword(s):  
Arabidopsis Thaliana ◽  
Green Fluorescent Protein ◽  
Protein Import ◽  
Fluorescent Protein ◽  
Protein Accumulation ◽  
Animal Development ◽  
Metabolic Reactions ◽  
Targeting Signals ◽  
Green Fluorescent ◽  
Peroxisome Targeting Signals

Peroxisomes compartmentalize certain metabolic reactions critical to plant and animal development. The import of proteins from the cytosol into the organelle matrix depends on more than a dozen peroxin (PEX) proteins, with PEX5 and PEX7 serving as receptors that shuttle proteins bearing one of two peroxisome-targeting signals (PTSs) into the organelle. PEX5 is the PTS1 receptor; PEX7 is the PTS2 receptor. In plants and mammals, PEX7 depends on PEX5 binding to deliver PTS2 cargo into the peroxisome. In this study, we characterized a pex7 missense mutation, pex7-2, that disrupts both PEX7 cargo binding and PEX7-PEX5 interactions in yeast, as well as PEX7 protein accumulation in plants. We examined localization of peroxisomally targeted green fluorescent protein derivatives in light-grown pex7 mutants and observed not only the expected defects in PTS2 protein import but also defects in PTS1 import. These PTS1 import defects were accompanied by reduced PEX5 accumulation in light-grown pex7 seedlings. Our data suggest that PEX5 and PTS1 import depend on the PTS2 receptor PEX7 in Arabidopsis and that the environment may influence this dependence. These data advance our understanding of the biogenesis of these essential organelles and provide a possible rationale for the retention of the PTS2 pathway in some organisms.

scholarly journals A Thioredoxin reductive mechanism balances the oxidative protein import pathway in the intermembrane space of mitochondria

2021 ◽  
Author(s):  
Mauricio Cardenas-Rodriguez ◽  
Phanee Manganas ◽  
Emmanouela Kallergi ◽  
Ruairidh Edwards ◽  
Afroditi Chatzi ◽  
...  
Keyword(s):  
Redox State ◽  
Protein Import ◽  
Interaction Analysis ◽  
Oxidative Capacity ◽  
Intermembrane Space ◽  
Thioredoxin System ◽  
In Vitro Reconstitution ◽  
Mitochondrial Intermembrane Space ◽  
Mitochondria Biogenesis

Mitochondria biogenesis crucially depends on the oxidative folding system in the mitochondrial intermembrane space. The oxidative capacity needs however to be balanced by a reductive pathway for optimal mitochondrial fitness. Here we report that the cytosolic thioredoxin machinery fulfils this critical reductive function by dual localisation in the mitochondrial intermembrane space (IMS) via an unconventional import pathway. We show that the presence of the Thioredoxin system in the IMS mediates a hitherto unknown communication between mitochondria biogenesis and the metabolic state of the cell via the cytosolic pool of NADPH. By a combination of complete in vitro reconstitution with purified components, import assays and protein interaction analysis we find that the IMS-localised thioredoxin machinery critically controls the redox state of Mia40, the key player in the MIA pathway in mitochondria thereby ensuring optimal mitochondria biogenesis. Intriguingly, we find that the IMS thioredoxin system fulfils a previously unknown role in the retrograde release of structurally destabilised proteins into the cytosol and protection against oxidative damage, both of which serve as critical mechanisms of mitochondrial surveillance and quality control.

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