Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of ...mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria.
Effects of lipids on mitochondrial functions Mårtensson, Christoph U.; Doan, Kim Nguyen; Becker, Thomas
Biochimica et biophysica acta. Molecular and cell biology of lipids,
January 2017, 2017-Jan, 2017-01-00, 20170101, Letnik:
1862, Številka:
1
Journal Article
Recenzirano
Mitochondria contain two membranes: the outer and inner membrane. Whereas the outer membrane is particularly enriched in phospholipids, the inner membrane has an unusual high protein content and ...forms large invaginations termed cristae. The proper phospholipid composition of the membranes is crucial for mitochondrial functions. Phospholipids affect activity, biogenesis and stability of protein complexes including protein translocases and respiratory chain supercomplexes. Negatively charged phospholipids such as cardiolipin are important for the architecture of the membranes and recruit soluble factors to the membranes to support mitochondrial dynamics. Thus, phospholipids not only form the hydrophobic core of biological membranes that surround mitochondria, but also create a specific environment to promote functions of various protein machineries. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.
•Phospholipids play central roles in diverse mitochondrial functions.
Phospholipids affect activity and stability of respiratory chain supercomplexes.•Mitochondrial protein translocases are closely linked to phospholipid homeostasis.•Phospholipids contribute to mitochondrial fusion and fission.•Cardiolipin supports the architecture of mitochondrial membranes.
Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the ...need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance.
Our working group conducted a situation analysis of the current patterns and determinants of antibiotic use and resistance in Viet Nam. International publications and local reports published between 1-1-1990 and 31-8-2012 were reviewed. All stakeholders analyzed the findings at a policy workshop and feasible recommendations were suggested to improve antibiotic use in Viet Nam.Here we report the results of our situation analysis focusing on: the healthcare system, drug regulation and supply; antibiotic resistance and infection control; and agricultural antibiotic use.
Market reforms have improved healthcare access in Viet Nam and contributed to better health outcomes. However, increased accessibility has been accompanied by injudicious antibiotic use in hospitals and the community, with predictable escalation in bacterial resistance. Prescribing practices are poor and self-medication is common - often being the most affordable way to access healthcare. Many policies exist to regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal penicillin-resistance rates are the highest in Asia and carbapenem-resistant bacteria (notably NDM-1) have recently emerged. Hospital acquired infections, predominantly with multi-drug resistant Gram-negative organisms, place additional strain on limited resources. Widespread agricultural antibiotic use further propagates antimicrobial resistance.
Future legislation regarding antibiotic access must alter incentives for purchasers and providers and ensure effective enforcement. The Ministry of Health recently initiated a national action plan and approved a multicenter health improvement project to strengthen national capacity for antimicrobial stewardship in Viet Nam. This analysis provided important input to these initiatives. Our methodologies and findings may be of use to others across the world tackling the growing threat of antibiotic resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this report, we summarize recent findings about a role of the outer membrane metabolite channel VDAC/porin in protein import into mitochondria. Mitochondria fulfill key functions for cellular ...energy metabolism. Their biogenesis involves the import of about 1000 different proteins that are produced as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the entry gate for mitochondrial precursor proteins. Dedicated protein translocases sort the preproteins into the different mitochondrial subcompartments. While protein transport pathways are analyzed to some detail, only little is known about regulatory mechanisms that fine-tune protein import upon metabolic signaling. Recently, a dual role of the voltage-dependent anion channel (VDAC), also termed porin, in mitochondrial protein biogenesis was reported. First, VDAC/porin promotes as a coupling factor import of carrier proteins into the inner membrane. Second, VDAC/porin regulates the formation of the TOM complex. Thus, the major metabolite channel in the outer membrane VDAC/porin connects protein import to mitochondrial metabolism.
In this study, three carbon-based solid acid catalysts were prepared
via
the one-step hydrothermal procedure using glucose and Brønsted acid, including sulfuric acid,
p
-toluenesulfonic acid, or ...hydrochloric acid. The as-synthesized catalysts were tested for their ability to convert cellulose into valuable chemicals. The effects of Brønsted acidic catalyst, catalyst loading, solvent, temperature, time, and reactor on the reaction were investigated. The as-synthesized C-H
2
SO
4
catalyst containing Brønsted acid sites (-SO
3
H, -OH, and -COOH functional groups) demonstrated high activity in the transformation of cellulose into valuable chemicals with the yield of total products of 88.17% including 49.79% LA in 1-ethyl-3-methylimidazolium chloride (EMIMCl) solvent at 120 °C in 24 h. The recyclability and stability of C-H
2
SO
4
were also observed. A proposed mechanism of cellulose conversion into valuable chemicals in the presence of C-H
2
SO
4
was presented. The current method could provide a feasible approach for the conversion of cellulose into valuable chemicals.
The conversion of cellulose to valuable chemicals using the catalytic system C-H
2
SO
4
/EMIMCl was reported for the first time. The yield of total products obtained was 88.17% (including 49.79% LA) under optimal conditions.
The mitochondrial inner membrane harbors a large number of metabolite carriers. The precursors of carrier proteins are synthesized in the cytosol and imported into mitochondria by the translocase of ...the outer membrane (TOM) and the carrier translocase of the inner membrane (TIM22). Molecular chaperones in the cytosol and intermembrane space bind to the hydrophobic precursors to prevent their aggregation. We report that the major metabolite channel of the outer membrane, termed porin or voltage-dependent anion channel (VDAC), promotes efficient import of carrier precursors. Porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring an efficient transfer of the precursors to the inner membrane translocase. Porin channel mutants impaired in metabolite transport are not disturbed in carrier import into mitochondria. We conclude that porin serves distinct functions as outer membrane channel for metabolites and as coupling factor for protein translocation into the inner membrane.
Display omitted
•Metabolite channel of mitochondrial outer membrane promotes protein import•Porin interacts with carrier precursors accumulated in the intermembrane space•Porin recruits the carrier translocase of the inner mitochondrial membrane•Dual role of porin as metabolite channel and as coupling factor in protein import
Ellenrieder et al. report that the major metabolite channel porin of the mitochondrial outer membrane promotes the import of carrier proteins to the mitochondrial inner membrane. Porin binds carrier precursors in the intermembrane space and recruits the carrier translocase of the inner membrane to facilitate transfer of the precursor proteins.
Spirulina/Arthrospira
is well known as a microscopic filamentous cyanobacterium, which is rich in nutrition and minerals. Therefore,
Spirulina/Arthrospira
cultivation industry has been adopting many ...optimization methods for enhancing biomass productivity. Recently, machine learning has been an emerging approach thanks to their efficacy. In this paper, a novel time-dependent reinforcement learning (RL) method with state prediction by long short-term memory (LSTM) networks is proposed to optimize the dry-weight yield of
Spirulina
sp. HH cultivation. The simulation results show that under the same light condition, with the proposed algorithm, the
Spirulina
sp. HH cultivation system produces a yield 17% higher than that of the traditional cultivation method and 10% higher than that of the threshold-based method. The results of the RL method from this study promise a significant benefit in
Spirulina
farm production when applying it for proactively planning biomass production and enhancing profit.
Graphical abstract
12 triterpenoid–AZT conjugates with cytotoxic activity were prepared via click chemistry. Display omitted
Betulinic acid and analogous naturally occurring triterpenoid acids were transformed into the ...corresponding propargyl esters and subsequently deployed as substrates for a click chemistry-mediated coupling with azidothymidine (AZT) en route to novel 1,2,3-triazole-tethered triterpenoid–AZT conjugates. Twelve new hybrids were thus prepared and assessed in terms of their cytotoxic activity, revealing an interesting anticancer activity of five triterpenoid–AZT hybrids on KB and Hep-G2 tumor cell lines.
The mitochondrial outer membrane contains integral proteins with α-helical membrane anchors or a transmembrane β-barrel. The translocase of the outer membrane (TOM) cooperates with the sorting and ...assembly machinery (SAM) in the import of β-barrel proteins, whereas the mitochondrial import (MIM) complex inserts precursors of multi-spanning α-helical proteins. Single-spanning proteins constitute more than half of the integral outer membrane proteins; however, their biogenesis is poorly understood. We report that the yeast MIM complex promotes the insertion of proteins with N-terminal (signal-anchored) or C-terminal (tail-anchored) membrane anchors. The MIM complex exists in three dynamic populations. MIM interacts with TOM to accept precursor proteins from the receptor Tom70. Free MIM complexes insert single-spanning proteins that are imported in a Tom70-independent manner. Finally, coupling of MIM and SAM promotes early assembly steps of TOM subunits. We conclude that the MIM complex is a major and versatile protein translocase of the mitochondrial outer membrane.
Display omitted
•Mitochondrial MIM complex as main translocase for α-helical outer membrane proteins•The MIM complex promotes import of signal-anchored and tail-anchored proteins•The MIM complex forms three dynamic populations•MIM and SAM complexes cooperate in the assembly of the TOM complex
Doan et al. report that the mitochondrial import (MIM) complex constitutes the major import site for single-spanning and multi-spanning outer membrane proteins. MIM exists in three forms and dynamically cooperates with outer membrane protein translocases to import different types of precursor proteins.
Coral Mucus Is a Hot Spot for Viral Infections Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry ...
Applied and environmental microbiology,
09/2015, Letnik:
81, Številka:
17
Journal Article
Recenzirano
Odprti dostop
There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined ...the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms.
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