scholarly journals Krebs Cycle Moonlights in Caspase Regulation

2016 ◽  
Vol 37 (1) ◽  
pp. 1-2 ◽  
Author(s):  
Adi Minis ◽  
Hermann Steller
Keyword(s):  
Krebs Cycle ◽  
Caspase Regulation

Spatially restricting caspase activation

2016 ◽  
Vol 9 (423) ◽  
pp. ec86-ec86
Author(s):  
Annalisa M. VanHook
Keyword(s):  
Short Form ◽  
Krebs Cycle ◽  
Cysteine Proteases ◽  
Specific Form ◽  
Mitochondrial Outer Membrane ◽  
S2 Cells ◽  
Caspase Activation ◽  
Link Type ◽  
Caspase Family ◽  
Caspase Regulation

In addition to executing programmed cell death, members of the caspase family of cysteine proteases also mediate the degradation of organelles and other cellular structures (see Minis and Steller). As the interconnected spermatids of Drosophilamelanogaster differentiate into mature sperm, they undergo a caspase-dependent process called “individualization,” during which the spermatids are separated and most of their cytoplasm and organelles are degraded. Aram etal. found that the β subunit of the ATP-specific form of succinyl-CoA synthetase (A-Sβ), a component of the Krebs cycle, restricts caspase activity to areas immediately around mitochondria. In yeast two-hybrid assays and coimmunoprecipitation experiments with extracts from cultured Drosophila S2 cells, A-Sβ interacted with Cul3T and Klhl10, two components of the testis-specific form of the Cullin-RING ubiquitin ligase (CRL3) complex that activates caspases. Expression of a testis-specific, long isoform of A-Sβ (A-SβT) increased during spermatid individualization and was required for caspase activation during individualization. A-SβT activated the CRL3 complex when the complex was reconstituted in S2 cells or ectopically expressed in the eye. Whereas the somatic, short form of A-Sβ (A-SβS) localizes to the mitochondrial matrix, A-SβT was present on the mitochondrial outer membrane and recruited Cul3 and Klhl10 to the mitochondrial surface. The authors mapped the domains of A-SβT that mediated binding to CRL3 and showed that A-SβT competed with an endogenous CRL3 inhibitor for binding to CRL3. Thus, A-SβT limits CRL3 activation to the mitochondrial surface, which in turn restricts caspase activation to this location to ensure that mitochondria are eliminated without triggering death of the spermatid.L. Aram, T. Braun, C. Braverman, Y. Kaplan, L. Ravid, S. Levin-Zaidman, E. Arama, A Krebs cycle component limits caspase activation rate through mitochondrial surface restriction of CRL activation. Dev.Cell37, 15–33 (2016). [PubMed]A. Minis, H. Steller, Krebs cycle moonlights in caspase regulation. Dev.Cell37, 1–2 (2016). [PubMed]

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

2020 ◽  
Vol 21 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Khandan Ilkhani ◽  
Milad Bastami ◽  
Soheila Delgir ◽  
Asma Safi ◽  
Shahrzad Talebian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Metabolic Reprogramming ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Potential Biomarker ◽  
Close Relationship ◽  
Microenvironmental Factors

: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

scholarly journals MECHANISM OF FIXATION OF CARBON DIOXIDE IN THE KREBS CYCLE

1941 ◽  
Vol 139 (1) ◽  
pp. 483-484
Author(s):  
H.G. Wood ◽  
C.H. Werkman ◽  
Allan Hemingway ◽  
A.O. Nier
Keyword(s):  
Carbon Dioxide ◽  
Krebs Cycle ◽  
Fixation Of Carbon Dioxide

scholarly journals An integrated overview on the regulation of sperm metabolism (glycolysis-Krebs cycle-oxidative phosphorylation)

2021 ◽  
pp. 106805
Author(s):  
Fernando J. Peña ◽  
José M. Ortiz-Rodríguez ◽  
Gemma L. Gaitskell-Phillips ◽  
Maria C. Gil ◽  
Cristina Ortega-Ferrusola ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Krebs Cycle

scholarly journals Effects of Meal Fructose/Glucose Composition on Postprandial Glucose Appearance and Hepatic Glycogen Synthesis in Healthy Subjects

2021 ◽  
Vol 10 (4) ◽  
pp. 596
Author(s):  
Cristina Barosa ◽  
Rogério T. Ribeiro ◽  
Rita Andrade ◽  
João F. Raposo ◽  
John G. Jones
Keyword(s):  
Plasma Glucose ◽  
Healthy Subjects ◽  
Glycogen Synthesis ◽  
Krebs Cycle ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Metabolic Complications ◽  
Glucose Ratio ◽  
Dietary Fructose ◽  
P Sources

Dietary fructose overshadows glucose in promoting metabolic complications. Intestinal fructose metabolism (IFM) protects against these effects in rodents, by favoring gluconeogenesis, but the extent of IFM in humans is not known. We therefore aimed to infer the extent of IFM by comparing the contribution of dietary fructose to systemic glucose and hepatic glycogen appearance postprandially. Twelve fasting healthy subjects ingested two protein meals in random order, one supplemented with 50 g 5/95 fructose/glucose (LF) and the other with 50 g 55/45 fructose/glucose (HF). Sources of postprandial plasma glucose appearance and hepatic glycogen synthesis were determined with deuterated water. Plasma glucose excursions, as well as pre- and post-meal insulin, c-peptide, and triglyceride levels were nearly identical for both meals. The total gluconeogenic contribution to plasma glucose appearance was significantly higher for HF versus LF (65 ± 2% vs. 34 ± 3%, p < 0.001). For HF, Krebs cycle anaplerosis accounted for two-thirds of total gluconeogenesis (43 ± 2%) with one-third from Triose-P sources (22 ± 1%). With LF, three-quarters of the total gluconeogenic contribution originated via Krebs cycle anaplerosis (26 ± 2%) with one-quarter from Triose-P sources (9 ± 2%). HF and LF gave similar direct and indirect pathway contributions to hepatic glycogen synthesis. Increasing the fructose/glucose ratio had significant effects on glucose appearance sources but no effects on hepatic glycogen synthesis sources, consistent with extensive IFM. The majority of fructose carbons were converted to glucose via the Krebs cycle.

The Calorimetric-respirometric Ratio: Its Potential as a Cytotoxicity Test

1994 ◽  
Vol 22 (5) ◽  
pp. 364-376
Author(s):  
Richard B. Kemp ◽  
Catherine Stephansen ◽  
Sajid Mohamed ◽  
R.W. John Meredith
Keyword(s):  
Heat Flux ◽  
Salt Solution ◽  
Krebs Cycle ◽  
Cytotoxicity Test ◽  
Antimycin A ◽  
Rich Medium ◽  
Animal Cells ◽  
Normal Input ◽  
High Level ◽  
L929 Mouse

The ratio between heat flux and oxygen flux, the calorimetric ratio, is an enthalpy budget device used to identify anaerobic pathways in the presence of respiration. Ratios that are more exothermic (i.e. more negative) than the average for catabolic substrates (-450kJ mol O2 ± 5%; Thornton's rule), are usual for cells established in culture, including suspension-adapted LS-L929 mouse fibroblasts. A common reason for this is a high level of glycolysis, to produce lactate, simultaneously with aerobic pathways. To test the idea that the calorimetric-respirometric (CR) ratio is a revealing cytotoxic endpoint, LS cells grown in serum-rich medium were insulted with known metabolic poisons. Malonate, 2,4-dinitrophenol (2,4-DNP) and a mixture of antimycin A and rotenone increased the CR ratio to degrees largely explained by greater lactate flux, the CR700 values being 22μM malonate, 56μM 2,4-DNP and, for the mixture, 2μM antimycin A and 5μM rotenone. Higher concentrations of 2,4-DNP gave an “exothermic gap” for which there was no explained pathway. Iodoacetate decreased the CR ratio while inhibiting glycolysis, a result which can be explained by the hypothesis that substrates available in the serum were degraded by mitochondrial pathways and thereby substituted for the normal input from the Krebs cycle, which had been arrested by pyruvate starvation. In a balanced salt solution containing only 5.5mM glucose, the metabolic rate slowed and the CR ratio was more exothermic (CR700 = 6μM), giving a “gap” for which there was no explanation. Ten MEIC chemicals gave CR700 endpoints which closely corresponded to the order of toxicity for a battery of tests using animal cells. The CR method thus provides a good basis for investigating the mechanisms by which chemicals have toxic effects on cells.

scholarly journals Isotopomer studies of gluconeogenesis and the Krebs cycle with 13C-labeled lactate.

1993 ◽  
Vol 268 (34) ◽  
pp. 25509-25521
Author(s):  
J Katz ◽  
P Wals ◽  
W N Lee
Keyword(s):  
Krebs Cycle
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