scholarly journals Mistargeting of hydrophobic mitochondrial proteins activates a nucleus-mediated posttranscriptional quality control pathway in trypanosomes

2021 ◽  
Author(s):  
Caroline E. Dewar ◽  
Silke Oeljeklaus ◽  
Jan Mani ◽  
Wignand W. D. Mühlhäuser ◽  
Bettina Warscheid ◽  
...  
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Import ◽  
Nuclear Protein ◽  
Mitochondrial Protein ◽  
Protein A ◽  
Mitochondrial Proteins ◽  
Mitochondrial Protein Import ◽  
Mitochondrial Quality Control ◽  
Import Receptor

Mitochondrial protein import in the parasitic protozoan Trypanosoma brucei is mediated by the atypical outer membrane translocase, ATOM. It consists of seven subunits including ATOM69, the import receptor for hydrophobic proteins. Ablation of ATOM69, but not of any other subunit, triggers a unique quality control pathway resulting in the proteasomal degradation of non-imported mitochondrial proteins. The process requires a protein of unknown function, an E3 ubiquitin ligase and the ubiquitin-like protein (TbUbL1), which all are recruited to the mitochondrion upon ATOM69 depletion. TbUbL1 is a nuclear protein, a fraction of which is released to the cytosol upon triggering of the pathway. Nuclear release is essential as cytosolic TbUbL1 can bind mislocalised mitochondrial proteins and likely transfers them to the proteasome. Mitochondrial quality control has previously been studied in yeast and metazoans. Finding such a pathway in the highly diverged trypanosomes suggests such pathways are an obligate feature of all mitochondria.

scholarly journals Structural Basis of Presequence Recognition by the Mitochondrial Protein Import Receptor Tom20

Cell ◽  
2000 ◽  
Vol 100 (5) ◽  
pp. 551-560 ◽  
Author(s):  
Yoshito Abe ◽  
Toshihiro Shodai ◽  
Takanori Muto ◽  
Katsuyoshi Mihara ◽  
Hisayoshi Torii ◽  
...  
Keyword(s):  
Protein Import ◽  
Mitochondrial Protein ◽  
Structural Basis ◽  
Mitochondrial Protein Import ◽  
Import Receptor

scholarly journals Inactivation of the Neurospora crassa gene encoding the mitochondrial protein import receptor MOM19 by the technique of "sheltered RIP".

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 107-118 ◽  
Author(s):  
T A Harkness ◽  
R L Metzenberg ◽  
H Schneider ◽  
R Lill ◽  
W Neupert ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Target Gene ◽  
Protein Import ◽  
Selectable Marker ◽  
Mitochondrial Protein ◽  
Mutant Gene ◽  
Mitochondrial Protein Import ◽  
Gene Encoding ◽  
Precursor Proteins ◽  
Import Receptor

Abstract We have used a technique referred to as "sheltered RIP" (repeat induced point mutation) to create mutants of the mom-19 gene of Neurospora crassa, which encodes an import receptor for nuclear encoded mitochondrial precursor proteins. Sheltered RIP permits the isolation of a mutant gene in one nucleus, even if that gene is essential for the survival of the organism, by sheltering the nucleus carrying the mutant gene in a heterokaryon with an unaffected nucleus. Furthermore, the nucleus harboring the RIPed gene contains a selectable marker so that it is possible to shift nuclear ratios in the heterokaryons to a state in which the nucleus containing the RIPed gene predominates in cultures grown under selective conditions. This results in a condition where the target gene product should be present at very suboptimal levels and allows the study of the mutant phenotype. One allele of mom-19 generated by this method contains 44 transitions resulting in 18 amino acid substitutions. When the heterokaryon containing this allele was grown under conditions favoring the RIPed nucleus, no MOM19 protein was detectable in the mitochondria of the strain. Homokaryotic strains containing the RIPed allele exhibit a complex and extremely slow growth phenotype suggesting that the product of the mom-19 gene is important in N. crassa.

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.

Msp1/ATAD1 in Protein Quality Control and Regulation of Synaptic Activities

2020 ◽  
Vol 36 (1) ◽  
pp. 141-164
Author(s):  
Lan Wang ◽  
Peter Walter
Keyword(s):  
Quality Control ◽  
Mitochondrial Membrane ◽  
Protein Import ◽  
Protein Quality ◽  
Atp Hydrolysis ◽  
Mitochondrial Protein ◽  
Neurotransmitter Receptors ◽  
Functional Specialization ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Protein Import

Mitochondrial function depends on the efficient import of proteins synthesized in the cytosol. When cells experience stress, the efficiency and faithfulness of the mitochondrial protein import machinery are compromised, leading to homeostatic imbalances and damage to the organelle. Yeast Msp1 (mitochondrial sorting of proteins 1) and mammalian ATAD1 (ATPase family AAA domain–containing 1) are orthologous AAA proteins that, fueled by ATP hydrolysis, recognize and extract mislocalized membrane proteins from the outer mitochondrial membrane. Msp1 also extracts proteins that have become stuck in the import channel. The extracted proteins are targeted for proteasome-dependent degradation or, in the case of mistargeted tail-anchored proteins, are given another chance to be routed correctly. In addition, ATAD1 is implicated in the regulation of synaptic plasticity, mediating the release of neurotransmitter receptors from postsynaptic scaffolds to allow their trafficking. Here we discuss how structural and functional specialization imparts the unique properties that allow Msp1/ATAD1 ATPases to fulfill these diverse functions and also highlight outstanding questions in the field.

scholarly journals Mitochondrial protein import: An unexpected disulfide bond

2016 ◽  
Vol 214 (4) ◽  
pp. 363-365 ◽  
Author(s):  
Dejana Mokranjac
Keyword(s):  
Disulfide Bond ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Channel Gating ◽  
Mitochondrial Proteins ◽  
Mitochondrial Protein Import ◽  
Cell Biol ◽  
Molecular Nature

Most mitochondrial proteins are imported through the TIM23 translocation channel, the structure and molecular nature of which are still unclear. In this issue, Ramesh et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602074) show that the TIM23 subunit Tim17 contains a disulfide bond that is crucial for protein translocation and channel gating.

scholarly journals From cytosol to mitochondria: the beginning of a protein journey

2020 ◽  
Vol 401 (6-7) ◽  
pp. 645-661 ◽  
Author(s):  
Maria Clara Avendaño-Monsalve ◽  
José Carlos Ponce-Rojas ◽  
Soledad Funes
Keyword(s):  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Protein Import ◽  
Protein Targeting ◽  
Mitochondrial Protein ◽  
Past Research ◽  
Membrane Receptors ◽  
Mitochondrial Proteins ◽  
Mitochondrial Protein Import ◽  
The Past

AbstractMitochondrial protein import is one of the key processes during mitochondrial biogenesis that involves a series of events necessary for recognition and delivery of nucleus-encoded/cytosol-synthesized mitochondrial proteins into the organelle. The past research efforts have mainly unraveled how membrane translocases ensure the correct protein sorting within the different mitochondrial subcompartments. However, early steps of recognition and delivery remain relatively uncharacterized. In this review, we discuss our current understanding about the signals on mitochondrial proteins, as well as in the mRNAs encoding them, which with the help of cytosolic chaperones and membrane receptors support protein targeting to the organelle in order to avoid improper localization. In addition, we discuss recent findings that illustrate how mistargeting of mitochondrial proteins triggers stress responses, aiming to restore cellular homeostasis.

Contractile activity-induced adaptations in the mitochondrial protein import system

1998 ◽  
Vol 274 (5) ◽  
pp. C1380-C1387 ◽  
Author(s):  
Mark Takahashi ◽  
Alan Chesley ◽  
Damien Freyssenet ◽  
David A. Hood
Keyword(s):  
Outer Membrane ◽  
Malate Dehydrogenase ◽  
Mitochondrial Biogenesis ◽  
Protein Import ◽  
Contractile Activity ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import ◽  
The Matrix ◽  
Stimulating Factor ◽  
Import Receptor

We previously demonstrated that subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial subfractions import proteins at different rates. This study was undertaken to investigate 1) whether protein import is altered by chronic contractile activity, which induces mitochondrial biogenesis, and 2) whether these two subfractions adapt similarly. Using electrical stimulation (10 Hz, 3 h/day for 7 and 14 days) to induce contractile activity, we observed that malate dehydrogenase import into the matrix of the SS and IMF mitochondia isolated from stimulated muscle was significantly increased by 1.4- to 1.7-fold, although the pattern of increase differed for each subfraction. This acceleration of import may be mitochondrial compartment specific, since the import of Bcl-2 into the outer membrane was not affected. Contractile activity also modified the mitochondrial content of proteins comprising the import machinery, as evident from increases in the levels of the intramitochondrial chaperone mtHSP70 as well as the outer membrane import receptor Tom20 in SS and IMF mitochondria. Addition of cytosol isolated from stimulated or control muscles to the import reaction resulted in similar twofold increases in the ability of mitochondria to import malate dehydrogenase, despite elevations in the concentration of mitochondrial import-stimulating factor within the cytosol of chronically stimulated muscle. These results suggest that chronic contractile activity modifies the extra- and intramitochondrial environments in a fashion that favors the acceleration of precursor protein import into the matrix of the organelle. This increase in protein import is likely an important adaptation in the overall process of mitochondrial biogenesis.

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