The ER chaperone calnexin controls mitochondrial positioning and respiration

2020 ◽  
Vol 13 (638) ◽  
pp. eaax6660 ◽  
Author(s):  
Tomás Gutiérrez ◽  
Hong Qi ◽  
Megan C. Yap ◽  
Nasser Tahbaz ◽  
Leanne A. Milburn ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Energy Balance ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Redox State ◽  
Glycolytic Pathway ◽  
Mitochondrial Bioenergetics ◽  
Cellular Energy ◽  
Er Chaperone ◽  
Oxidative Phosphorylation Pathway

Chaperones in the endoplasmic reticulum (ER) control the flux of Ca2+ ions into mitochondria, thereby increasing or decreasing the energetic output of the oxidative phosphorylation pathway. An example is the abundant ER lectin calnexin, which interacts with sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). We found that calnexin stimulated the ATPase activity of SERCA by maintaining its redox state. This function enabled calnexin to control how much ER Ca2+ was available for mitochondria, a key determinant for mitochondrial bioenergetics. Calnexin-deficient cells compensated for the loss of this function by partially shifting energy generation to the glycolytic pathway. These cells also showed closer apposition between the ER and mitochondria. Calnexin therefore controls the cellular energy balance between oxidative phosphorylation and glycolysis.

scholarly journals Mitochondrial protein gene expression and the oxidative phosphorylation pathway associated with feed efficiency and energy balance in dairy cattle

2021 ◽  
Vol 104 (1) ◽  
pp. 575-587
Author(s):  
Jigme Dorji ◽  
Iona M. MacLeod ◽  
Amanda J. Chamberlain ◽  
Christy J. Vander Jagt ◽  
Phuong N. Ho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Oxidative Phosphorylation ◽  
Dairy Cattle ◽  
Feed Efficiency ◽  
Protein Gene ◽  
Mitochondrial Protein ◽  
Oxidative Phosphorylation Pathway

scholarly journals Hepatic endosome fractions contain an ATP-driven proton pump

1985 ◽  
Vol 225 (1) ◽  
pp. 51-58 ◽  
Author(s):  
T Saermark ◽  
N Flint ◽  
W H Evans
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Atpase Activity ◽  
Proton Pump ◽  
Subcellular Distribution ◽  
Plasma Membranes ◽  
Specific Activity ◽  
Ph Gradients ◽  
Subcellular Organelle ◽  
Liver Homogenates

Endosome fractions were isolated from rat liver homogenates on the basis of the subcellular distribution of circulating ligands, e.g. 125I-asialotransferrin internalized by hepatocytes by a receptor-mediated process. The distribution of endocytosed 125I-asialotransferrin 1-2 min and 15 min after uptake by liver and a monensin-activated Mg2+-dependent ATPase activity coincided on linear gradients of sucrose and Nycodenz. The monensin-activated Mg2+-ATPase was enriched relative to the liver homogenates up to 60-fold in specific activity in the endosome fractions. Contamination of the endosome fractions by lysosomes, endoplasmic reticulum, mitochondria, plasma membranes and Golgi-apparatus components was low. By use of 9-aminoacridine, a probe for pH gradients, the endosome vesicles were shown to acidify on addition of ATP. Acidification was reversed by addition of monensin. The results indicate that endosome fractions contain an ATP-driven proton pump. The ionophore-activated Mg2+-ATPase in combination with the presence of undegraded ligands in the endosome fractions emerge as linked markers for this new subcellular organelle.

scholarly journals Degradation of aggrecan precursors within a specialized subcompartment of the chicken chondrocyte endoplasmic reticulum

1996 ◽  
Vol 316 (2) ◽  
pp. 487-495 ◽  
Author(s):  
Manuel ALONSO ◽  
Josefina HIDALGO ◽  
Linda HENDRICKS ◽  
Angel VELASCO
Keyword(s):  
Endoplasmic Reticulum ◽  
Protease Inhibitors ◽  
Degradation Rate ◽  
Redox State ◽  
Brefeldin A ◽  
Lag Phase ◽  
Cysteine Protease Inhibitors ◽  
Immunofluorescence Analysis ◽  
Smooth Membrane ◽  
Membrane Bound

Chicken chondrocytes in culture synthesize aggrecan proteoglycan as a 370 kDa precursor that is glycosylated and secreted into the medium with a half-life of 30 min. In metabolic studies the 370 kDa precursor was shown to render a degradation intermediate of 190 kDa, which appeared with no measurable lag phase; it was dependent on temperature (> 20 °C) and inhibited by certain serine and serine/cysteine protease inhibitors such as leupeptin and PMSF. By contrast, degradation was unaffected by treatment of the cells with brefeldin A or with lysosomotropic agents. Aggrecan precursors were detected by immunofluorescence analysis within a subcompartment of the endoplasmic reticulum (ER), previously characterized as a smooth-membrane-bound subregion [Vertel, Velasco, LaFrance, Walters and Kaczman-Daniel (1989) J. Cell Biol. 109, 1827–1836]. Analysis of the subcellular fractions derived from chondrocytes indicated that the degradation intermediate was concentrated in the ER subcompartment. Degradation was dependent on the Ca2+ concentration and the redox state in the ER. Treatment of the cells with agents or conditions that alter the degradation rate of aggrecan precursors, such as protease inhibitors, decreased temperature or dithiothreitol, also modified the retention of these molecules in the ER subcompartment, as seen by immunofluorescence. These results indicate that a fraction of the 370 kDa aggrecan precursor is targeted to a smooth ER subcompartment where it undergoes degradation.

Oxidative protein folding in the mammalian endoplasmic reticulum

2004 ◽  
Vol 32 (5) ◽  
pp. 655-658 ◽  
Author(s):  
C.E. Jessop ◽  
S. Chakravarthi ◽  
R.H. Watkins ◽  
N.J. Bulleid
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Redox State ◽  
Structure And Function ◽  
Reduced Form ◽  
Secretory Proteins ◽  
Oxidative Protein Folding ◽  
Disulphide Bonds ◽  
And Function ◽  
Substrate Proteins

Native disulphide bonds are essential for the structure and function of many membrane and secretory proteins. Disulphide bonds are formed, reduced and isomerized in the endoplasmic reticulum of mammalian cells by a family of oxidoreductases, which includes protein disulphide isomerase (PDI), ERp57, ERp72, P5 and PDIR. This review will discuss how these enzymes are maintained in either an oxidized redox state that allows them to form disulphide bonds in substrate proteins or a reduced form that allows them to perform isomerization and reduction reactions, how these opposing pathways may co-exist within the same compartment and why so many oxidoreductases exist when PDI alone can perform all three of these functions.

Control of cell shape by calcium in the euglenophyceae

1981 ◽  
Vol 49 (1) ◽  
pp. 99-117 ◽  
Author(s):  
J.M. Murray
Keyword(s):  
Endoplasmic Reticulum ◽  
Atpase Activity ◽  
Calcium Oxalate ◽  
Cell Shape ◽  
Motor Units ◽  
Astasia Longa ◽  
Oxalate Precipitation ◽  
Entire Cell ◽  
The Individual ◽  
Euglenoid Movement

The euglenoid flagellates are able to change their shape rapidly in response to a variety of stimuli, or sometimes spontaneously. Two extremes of shape can be identified: the “relaxed” form is cylindrical; the contracted form is a somewhat distorted disc. These 2 forms can be interconverted by treatments that alter the Ca2+ concentration of the entire cell. The level of Ca2+ is believed to be normally controlled by a system of calcium-accumulating membranes, identified in Astasia longa by the technique of calcium oxalate precipitation. The system forms a set of parallel tubes of endoplasmic reticulum, one of which lies immediately below each of the ridges of the pellicle. The individual ridges, each with its associated reticulum, microtubules and other elements are suggested to be independent motor units. Local activation of a small number of these units by Ca2+ is made possible by the arrangement of Ca2+ -sequestering reticulum, producing the characteristic squirming euglenoid movement. Uniform activation or suppression of all units produces the 2 extremes of shape. The pellicle of A. longa with its associated microtubules has been purified and shown to contain a Ca2+ -binding site and ATPase activity.

scholarly journals Partial diploids of Escherichia coli carrying normal and mutant alleles affecting oxidative phosphorylation

1977 ◽  
Vol 162 (3) ◽  
pp. 665-670 ◽  
Author(s):  
F Gibson ◽  
G B Cox ◽  
J A Downie ◽  
J Radik
Keyword(s):  
Escherichia Coli ◽  
Fluorescence Quenching ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Adenosine Triphosphatase ◽  
Growth Yields ◽  
Normal Allele ◽  
Adenosine Triphosphatase Activity

A plasmid was isolated which included the region of the Escherichia coli chromosome carrying the known genes concerned with oxidative phosphorylation (unc genes). This plasmid was used to prepare partial diploids carrying normal unc alleles on the episome and one of the three mutant alleles (unc A401, uncB402 or unc-405) on the chromosome. These strains were compared with segregants from which the plasmid had been lost. Dominance of either normal ormutant unc alleles was determined by growth on succinate, growth yields on glucose, Mg-ATPase (Mg2+-stimulated adenosine triphosphatase) activity, atebrin-fluorescence quenching, ATP-dependent transhydrogenase activity and oxidative phosphorylation. In all the above tests, dominance of the normal allele was observed. However, in membranes from the diploid strains which carried a normal allele and either of the mutant alleles affecting Mg-ATPase activity (uncA401 or unc-405), the energy-linked functions were only partially restored.

scholarly journals Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 337 ◽  
Author(s):  
Amruta Nayak ◽  
Arvinder Kapur ◽  
Lisa Barroilhet ◽  
Manish Patankar
Keyword(s):  
Ovarian Cancer ◽  
Oxidative Phosphorylation ◽  
Aerobic Glycolysis ◽  
Ovarian Tumors ◽  
Metabolic Adaptation ◽  
Ovarian Cancer Stem Cells ◽  
Critical Control Points ◽  
Energy Needs ◽  
Oxidative Phosphorylation Pathway ◽  
Novel Therapeutic Strategies

Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.

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