Electron Transfer Chain
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2021 ◽  
Author(s):  
Anna Schulten ◽  
Bjoern Pietzenuk ◽  
Julia Quintana ◽  
Marcus Krause ◽  
Regina Feil ◽  
...  

Copper (Cu) is a cofactor of around 300 Arabidopsis proteins including photosynthetic and mitochondrial electron transfer chain enzymes critical for ATP production and carbon fixation. Plant acclimation to Cu deficiency requires the transcription factor SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE7 (SPL7). We report that in the wild type and in the spl7-1 mutant, respiratory electron flux via Cu-dependent cytochrome c oxidase remained unaffected under both normal and low-Cu cultivation conditions. Contrary to the wild type, supplementing Cu-deficient media with exogenous sugar failed to stimulate growth of spl7-1. The spl7-1 mutant accumulated carbohydrates including the signaling sugar trehalose 6-phosphate, as well as ATP and NADH, also under normal Cu supply and without sugar supplementation. Late flowering of spl7 1 was in agreement with its attenuated sugar responsiveness. Functional TOR and SnRK1 kinase signaling in spl7-1 suggested against fundamental defects in these energy-signaling hubs. Sequencing of chromatin immunoprecipitates combined with transcriptomics identified direct targets of SPL7-mediated positive regulation, including FE SUPEROXIDE DISMUTASE1 (FSD1), COPPER-DEFICIENCY-INDUCED TRANSCRIPTION FACTOR1 (CITF1) and uncharacterized bHLH23 (CITF2), as well as an enriched upstream GTACTRC motif. In summary, transducing energy availability into growth and reproductive development requires the function of SPL7. Our results could help to increase crop yields, especially on Cu-deficient soils.


2021 ◽  
Author(s):  
Zhuoyang Lu ◽  
Tiantian Zhang ◽  
Yachong Hu ◽  
Hui Liu ◽  
Li Cui ◽  
...  

Abstract Cellular hydrostatic pressure beyond its normal range can induce the accumulation of reactive oxidative species (ROS) generated by mitochondria and lead to pathological conditions such as glaucomatous optic neuropathy. However, little is known about how the mitochondrial electron transfer chain (ETC) is affected by elevated pressure. Moreover, the protective effects of hydrogen on various pathological conditions have been observed by reductions in ROS, yet the role of hydrogen in high hydrostatic pressure (HHP)-induced cell damage remains obscure. The goal of this study was to investigate the effect of HHP on ETC activity and whether hydrogen exerts protective effects against HHP-induced damage in cultured neuronal cells. Cultured SH-SY5Y human neuroblastoma cells were exposed to an elevated ambient hydrostatic pressure of 50 mmHg for a period of 2 to 6 h. HHP impaired the activities of ETC complexes, and these effects were reversed by hydrogen. Significant increases in apoptotic rates and intracellular ROS levels were observed in HHP-treated SH-SY5Y cells. Hydrogen significantly inhibited the apoptotic rates and reduced the levels of ROS. These findings suggest that HHP induces cell damage by causing ETC dysfunction to increase oxidative stress and that hydrogen may act as a protective agent to alleviate HHP-induced neuronal injury.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1858
Author(s):  
Melisa Herrero ◽  
Maron Daw ◽  
Andrea Atzmon ◽  
Orna Elroy-Stein

Translation initiation factor 2B (eIF2B) is a master regulator of global protein synthesis in all cell types. The mild genetic Eif2b5(R132H) mutation causes a slight reduction in eIF2B enzymatic activity which leads to abnormal composition of mitochondrial electron transfer chain complexes and impaired oxidative phosphorylation. Previous work using primary fibroblasts isolated from Eif2b5(R132H/R132H) mice revealed that owing to increased mitochondrial biogenesis they exhibit normal cellular ATP level. In contrast to fibroblasts, here we show that primary astrocytes isolated from Eif2b5(R132H/R132H) mice are unable to compensate for their metabolic impairment and exhibit chronic state of low ATP level regardless of extensive adaptation efforts. Mutant astrocytes are hypersensitive to oxidative stress and to further energy stress. Moreover, they show migration deficit upon exposure to glucose starvation. The mutation in Eif2b5 prompts reactive oxygen species (ROS)-mediated inferior ability to stimulate the AMP-activated protein kinase (AMPK) axis, due to a requirement to increase the mammalian target of rapamycin complex-1 (mTORC1) signalling in order to enable oxidative glycolysis and generation of specific subclass of ROS-regulating proteins, similar to cancer cells. The data disclose the robust impact of eIF2B on metabolic and redox homeostasis programs in astrocytes and point at their hyper-sensitivity to mutated eIF2B. Thereby, it illuminates the central involvement of astrocytes in Vanishing White Matter Disease (VWMD), a genetic neurodegenerative leukodystrophy caused by homozygous hypomorphic mutations in genes encoding any of the 5 subunits of eIF2B.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3499
Author(s):  
Raquel Luna-Yolba ◽  
Justine Marmoiton ◽  
Véronique Gigo ◽  
Xavier Marechal ◽  
Emeline Boet ◽  
...  

Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the anti-tumor response. The modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve the therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as ectonucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemo-resistance and a poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased the OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that while AraC induced an immune response regulation by increasing CD39 expression and by reinforcing the interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.


2021 ◽  
Author(s):  
Jie Li ◽  
Hamza Sohail ◽  
Muhammad Azher Nawaz ◽  
Chaowei Liu ◽  
Ping Yang

Abstract Brassinosteroids (BRs) are important in plant resistance to chilling stress. However, limited information is available regarding the specific mechanisms involved at proteomic level. We utilized iTRAQ proteomic approach, physiological assays and information obtained from cellular ultrastructure to clarify the underlying molecular mechanism of BRs to alleviate chilling stress in pepper (Capsicum annuum L.). Foliar application of 24-epibrassinolide (EBR) improved photosynthesis and improved cell structure by presenting a distinct mesophyll cell and chloroplast with well-developed thylakoid membranes in the leaves of pepper seedlings. We identified 346 differentially expressed proteins (DEPs), including 217 up-regulated proteins and 129 down-regulated proteins in plants under chilling (Chill) and Chill + EBR treated plants. Most of the DEPs were related to multiple pathways, including photosynthesis, carbohydrates metabolism, energy metabolism, protein biosynthesis, amino acids synthesis, redox and stress defence (ascorbate peroxidase, glutathione peroxidase, and superoxide dismutase). Up-regulated DEPs were associated with photosynthetic electron transfer chain, oxidative phosphorylation, GSH metabolism pathway, Calvin cycle and signaling pathway. The physiochemical analysis showed that EBR treatment improved the tolerance of pepper seedlings to chilling stress.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hao Wu ◽  
Yuqi Wang ◽  
Minfeng Ying ◽  
Chengmeng Jin ◽  
Jiangtao Li ◽  
...  

AbstractPrevious studies demonstrated that superoxide could initiate and amplify LDH-catalyzed hydrogen peroxide production in aqueous phase, but its physiological relevance is unknown. Here we showed that LDHA and LDHB both exhibited hydrogen peroxide-producing activity, which was significantly enhanced by the superoxide generated from the isolated mitochondria from HeLa cells and patients’ cholangiocarcinoma specimen. After LDHA or LDHB were knocked out, hydrogen peroxide produced by Hela or 4T1 cancer cells were significantly reduced. Re-expression of LDHA in LDHA-knockout HeLa cells partially restored hydrogen peroxide production. In HeLa and 4T1 cells, LDHA or LDHB knockout or LDH inhibitor FX11 significantly decreased ROS induction by modulators of the mitochondrial electron transfer chain (antimycin, oligomycin, rotenone), hypoxia, and pharmacological ROS inducers piperlogumine (PL) and phenethyl isothiocyanate (PEITC). Moreover, the tumors formed by LDHA or LDHB knockout HeLa or 4T1 cells exhibited a significantly less oxidative state than those formed by control cells. Collectively, we provide a mechanistic understanding of a link between LDH and cellular hydrogen peroxide production or oxidative stress in cancer cells in vitro and in vivo.


Author(s):  
Christopher J. Gisriel ◽  
Chihiro Azai ◽  
Tanai Cardona

AbstractPhotosynthetic reaction centers (RC) catalyze the conversion of light to chemical energy that supports life on Earth, but they exhibit substantial diversity among different phyla. This is exemplified in a recent structure of the RC from an anoxygenic green sulfur bacterium (GsbRC) which has characteristics that may challenge the canonical view of RC classification. The GsbRC structure is analyzed and compared with other RCs, and the observations reveal important but unstudied research directions that are vital for disentangling RC evolution and diversity. Namely, (1) common themes of electron donation implicate a Ca2+ site whose role is unknown; (2) a previously unidentified lipid molecule with unclear functional significance is involved in the axial ligation of a cofactor in the electron transfer chain; (3) the GsbRC features surprising structural similarities with the distantly-related photosystem II; and (4) a structural basis for energy quenching in the GsbRC can be gleaned that exemplifies the importance of how exposure to oxygen has shaped the evolution of RCs. The analysis highlights these novel avenues of research that are critical for revealing evolutionary relationships that underpin the great diversity observed in extant RCs.


Author(s):  
Raquel Luna-Yolba ◽  
Justine Marmoiton ◽  
Véronique Gigo ◽  
Xavier Marechal ◽  
Emeline Boet ◽  
...  

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mingzhu Ma ◽  
Yifei Liu ◽  
Chunming Bai ◽  
Jean Wan Hong Yong

Chloroplast NAD(P)H dehydrogenase (NDH) complex, a multiple-subunit complex in the thylakoid membranes mediating cyclic electron transport, is one of the most important alternative electron transport pathways. It was identified to be essential for plant growth and development during stress periods in recent years. The NDH-mediated cyclic electron transport can restore the over-reduction in stroma, maintaining the balance of the redox system in the electron transfer chain and providing the extra ATP needed for the other biochemical reactions. In this review, we discuss the research history and the subunit composition of NDH. Specifically, the formation and significance of NDH-mediated cyclic electron transport are discussed from the perspective of plant evolution and physiological functionality of NDH facilitating plants’ adaptation to environmental stress. A better understanding of the NDH-mediated cyclic electron transport during photosynthesis may offer new approaches to improving crop yield.


2021 ◽  
Author(s):  
Komal Joshi ◽  
Chi Ho Chan ◽  
Daniel R. Bond

Geobacter sulfurreducens utilizes extracellular electron acceptors such as Mn(IV), Fe(III), syntrophic partners, and electrodes that vary from +0.4 to –0.3 V vs. Standard Hydrogen Electrode (SHE), representing a potential energy span that should require a highly branched electron transfer chain. Here we describe CbcBA, a bc-type cytochrome essential near the thermodynamic limit of respiration when acetate is the electron donor. Mutants lacking cbcBA ceased Fe(III) reduction –0.21 V vs. SHE, could not transfer electrons to electrodes between –0.21 and –0.28 V, and could not reduce the final 10% – 35% of Fe(III) minerals. As redox potential decreased during Fe(III) reduction, cbcBA was induced with the aid of the regulator BccR to become one of the most highly expressed genes in G. sulfurreducens. Growth yield (CFU/mM Fe(II)) was 112% of WT cbcBA, and deletion of cbcL (a different bc-cytochrome essential near –0.15 V) in ΔcbcBA increased yield to 220%. Together with ImcH, which is required at high redox potentials, CbcBA represents a third cytoplasmic membrane oxidoreductase in G. sulfurreducens. This expanding list shows how these important metal-reducing bacteria may constantly sense redox potential to adjust growth efficiency in changing environments.


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