scholarly journals Differential posttranslational modification of mitochondrial enzymes corresponds with metabolic suppression during hibernation

2019 ◽  
Vol 317 (2) ◽  
pp. R262-R269 ◽  
Author(s):  
Katherine E. Mathers ◽  
James F. Staples
Keyword(s):  
Body Temperature ◽  
Metabolic Rate ◽  
Posttranslational Modifications ◽  
Complex I ◽  
Tricarboxylic Acid Cycle ◽  
Mitochondrial Metabolism ◽  
Mitochondrial Proteins ◽  
Mitochondrial Enzymes ◽  
Two Dimensional ◽  
Complex Ii

During hibernation, small mammals, including the 13-lined ground squirrel ( Ictidomys tridecemlineatus), cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5°C, and interbout euthermia (IBE), where both metabolic rate and body temperature rapidly increase to euthermic levels. Suppression of whole animal metabolism during torpor is paralleled by rapid, reversible suppression of mitochondrial respiration. We hypothesized that these changes in mitochondrial metabolism are regulated by posttranslational modifications to mitochondrial proteins. Differential two-dimensional gel electrophoresis and two-dimensional blue-native PAGE revealed differences in the isoelectric point of several liver mitochondrial proteins between torpor and IBE. Quadrupole time-of-flight LC/MS and matrix-assisted laser desorption/ionization MS identified these as proteins involved in β-oxidation, the tricarboxylic acid cycle, reactive oxygen species detoxification, and the electron transport system (ETS). Immunoblots revealed that subunit 1 of ETS complex IV was acetylated during torpor but not IBE. Phosphoprotein staining revealed significantly greater phosphorylation of succinyl-CoA ligase and the flavoprotein subunit of ETS complex II in IBE than torpor. In addition, the 75-kDa subunit of ETS complex I was 1.5-fold more phosphorylated in torpor. In vitro treatment with alkaline phosphatase increased the maximal activity of complex I from liver mitochondria isolated from torpid, but not IBE, animals. By contrast, phosphatase treatment decreased complex II activity in IBE but not torpor. These findings suggest that the rapid changes in mitochondrial metabolism in hibernators are mediated by posttranslational modifications of key metabolic enzymes, perhaps by intramitochondrial kinases and deacetylases.

Mitochondrial Complex I Function Affects Halothane Sensitivity in Caenorhabditis elegans 

2004 ◽  
Vol 101 (2) ◽  
pp. 365-372 ◽  
Author(s):  
Ernst-Bernhard Kayser ◽  
Phil G. Morgan ◽  
Margaret M. Sedensky
Keyword(s):  
Caenorhabditis Elegans ◽  
Oxidative Phosphorylation ◽  
Oxidative Damage ◽  
Adenosine Triphosphate ◽  
Complex I ◽  
Volatile Anesthetics ◽  
Mitochondrial Proteins ◽  
Wild Type ◽  
Complex Ii ◽  
C Elegans

Background : The gene gas-1 encodes a subunit of complex I of the mitochondrial electron transport chain in Caenorhabditis elegans. A mutation in gas-1 profoundly increases sensitivity of C. elegans to volatile anesthetics. It is unclear which aspects of mitochondrial function account for the hypersensitivity of the mutant. Methods : Oxidative phosphorylation was determined by measuring mitochondrial oxygen consumption using electron donors specific for either complex I or complex II. Adenosine triphosphate concentrations were determined by measuring luciferase activity. Oxidative damage to mitochondrial proteins was identified using specific antibodies. Results : Halothane inhibited oxidative phosphorylation in isolated wild-type mitochondria within a concentration range that immobilizes intact worms. At equal halothane concentrations, complex I activity but not complex II activity was lower in mitochondria from mutant (gas-1) animals than from wild-type (N2) animals. The halothane concentrations needed to immobilize 50% of N2 or gas-1 animals, respectively, did not reduce oxidative phosphorylation to identical rates in the two strains. In air, adenosine triphosphate concentrations were similar for N2 and gas-1 but were decreased in the presence of halothane only in gas-1 animals. Oxygen tension changed the sensitivity of both strains to halothane. When nematodes were raised in room air, oxidative damage to mitochondrial proteins was increased in the mutant animal compared with the wild type. Conclusions : Rates of oxidative phosphorylation and changes in adenosine triphosphate concentrations by themselves do not control anesthetic-induced immobility of wild-type C. elegans. However, they may contribute to the increased sensitivity to volatile anesthetics of the gas-1 mutant. Oxidative damage to proteins may be an important contributor to sensitivity to volatile anesthetics in C. elegans.

scholarly journals Platelet Mitochondrial Complex I and I+III Activities Do Not Correlate with Cerebral Mitochondrial Oxidative Metabolism

2010 ◽  
Vol 31 (1) ◽  
pp. e1-e5 ◽  
Author(s):  
William J Powers ◽  
Richard H Haas ◽  
Thuy Le ◽  
Tom O Videen ◽  
Joanne Markham ◽  
...  
Keyword(s):  
Metabolic Rate ◽  
Oxidative Metabolism ◽  
Complex I ◽  
Mitochondrial Metabolism ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Ets Activity ◽  
Cerebral Metabolic Rate ◽  
Glucose Ratio ◽  
Mitochondrial Oxidative Metabolism

Assays of mitochondrial electron transport system (ETS) activity in circulating blood platelets have been used to investigate the cause of neurodegenerative diseases. However, the correspondence between platelet ETS function and cerebral mitochondrial metabolism is not well characterized. To assess the validity of using platelet ETS activity to infer cerebral mitochondrial metabolism, we measured platelet ETS activity (complex I and complex I+III), cerebral metabolic rate of oxygen (CMRO2), and the CMRO2/cerebral metabolic rate for glucose ratio in 40 subjects: 7 with never-medicated Parkinson's disease, 13 with genetically proved Huntington's disease, and 20 normal controls. We found no correlation between in vivo measures of cerebral mitochondrial oxidative metabolism and ex vivo assays of platelet complex I and complex I+III activity performed on blood collected immediately before cerebral metabolism studies. We saw no evidence of a threshold effect when comparing platelet complex I and complex I+III activity with cerebral oxidative metabolism across a 4- to 10-fold range of platelet ETS activity. On the basis of these data, we conclude that measures of mitochondrial complex I and I+III activity in platelets within the ranges we have studied do not correlate with oxidative function of cerebral mitochondria.

scholarly journals ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hayley I. Muendlein ◽  
Wilson M. Connolly ◽  
Zoie Magri ◽  
Irina Smirnova ◽  
Vladimir Ilyukha ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Complex Formation ◽  
Complex I ◽  
Yersinia Pseudotuberculosis ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Inflammatory Signaling ◽  
Complex Ii ◽  
Dependent Model

AbstractInflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.

scholarly journals The decoupled nature of basal metabolic rate and body temperature in endotherm evolution

Nature ◽  
2019 ◽  
Vol 572 (7771) ◽  
pp. 651-654 ◽  
Author(s):  
Jorge Avaria-Llautureo ◽  
Cristián E. Hernández ◽  
Enrique Rodríguez-Serrano ◽  
Chris Venditti
Keyword(s):  
Body Temperature ◽  
Metabolic Rate ◽  
Basal Metabolic Rate

scholarly journals Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shirley Tremel ◽  
Yohei Ohashi ◽  
Dustin R. Morado ◽  
Jessie Bertram ◽  
Olga Perisic ◽  
...  
Keyword(s):  
Complex I ◽  
Kinase Domain ◽  
Beclin 1 ◽  
Structural Basis ◽  
Rab Gtpases ◽  
Lipid Kinase ◽  
Complex Ii ◽  
Cellular Processes ◽  
Specific Complex ◽  
Electron Cryotomography

AbstractThe lipid phosphatidylinositol-3-phosphate (PI3P) is a regulator of two fundamental but distinct cellular processes, endocytosis and autophagy, so its generation needs to be under precise temporal and spatial control. PI3P is generated by two complexes that both contain the lipid kinase VPS34: complex II on endosomes (VPS34/VPS15/Beclin 1/UVRAG), and complex I on autophagosomes (VPS34/VPS15/Beclin 1/ATG14L). The endosomal GTPase Rab5 binds complex II, but the mechanism of VPS34 activation by Rab5 has remained elusive, and no GTPase is known to bind complex I. Here we show that Rab5a–GTP recruits endocytic complex II to membranes and activates it by binding between the VPS34 C2 and VPS15 WD40 domains. Electron cryotomography of complex II on Rab5a-decorated vesicles shows that the VPS34 kinase domain is released from inhibition by VPS15 and hovers over the lipid bilayer, poised for catalysis. We also show that the GTPase Rab1a, which is known to be involved in autophagy, recruits and activates the autophagy-specific complex I, but not complex II. Both Rabs bind to the same VPS34 interface but in a manner unique for each. These findings reveal how VPS34 complexes are activated on membranes by specific Rab GTPases and how they are recruited to unique cellular locations.

scholarly journals In female rat heart mitochondria, oophorectomy results in loss of oxidative phosphorylation

2017 ◽  
Vol 232 (2) ◽  
pp. 221-235 ◽  
Author(s):  
Natalia Pavón ◽  
Alfredo Cabrera-Orefice ◽  
Juan Carlos Gallardo-Pérez ◽  
Cristina Uribe-Alvarez ◽  
Nadia A Rivero-Segura ◽  
...  
Keyword(s):  
Rat Heart ◽  
Complex I ◽  
Adenine Nucleotide ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Enzymes ◽  
Female Rat ◽  
Adult Rats ◽  
Mitochondrial Alterations ◽  
Rat Heart Mitochondria ◽  
Estrogen Depletion

Oophorectomy in adult rats affected cardiac mitochondrial function. Progression of mitochondrial alterations was assessed at one, two and three months after surgery: at one month, very slight changes were observed, which increased at two and three months. Gradual effects included decrease in the rates of oxygen consumption and in respiratory uncoupling in the presence of complex I substrates, as well as compromised Ca2+ buffering ability. Malondialdehyde concentration increased, whereas the ROS-detoxifying enzyme Mn2+ superoxide dismutase (MnSOD) and aconitase lost activity. In the mitochondrial respiratory chain, the concentration and activity of complex I and complex IV decreased. Among other mitochondrial enzymes and transporters, adenine nucleotide carrier and glutaminase decreased. 2-Oxoglutarate dehydrogenase and pyruvate dehydrogenase also decreased. Data strongly suggest that in the female rat heart, estrogen depletion leads to progressive, severe mitochondrial dysfunction.

Relationship between metabolic rate and core body temperature during sleep in human

2015 ◽  
Vol 16 ◽  
pp. S186-S187 ◽  
Author(s):  
I. Park ◽  
M. Kayaba ◽  
K. Iwayama ◽  
H. Ogata ◽  
Y. Sengoku ◽  
...  
Keyword(s):  
Body Temperature ◽  
Metabolic Rate ◽  
Core Body Temperature ◽  
Core Body

On the Regulation of the Respiration in Reptiles

1961 ◽  
Vol 38 (2) ◽  
pp. 301-314 ◽  
Author(s):  
BODIL NIELSEN
Keyword(s):  
Steady State ◽  
Body Temperature ◽  
Metabolic Rate ◽  
Temperature Interval ◽  
Normal Values ◽  
Pulmonary Ventilation ◽  
The Body ◽  
Respiratory Frequency ◽  
Temperature Changes ◽  
Instantaneous Increase

1. In two species of Lacerta (L. viridis and L. sicula) the effects on respiration of body temperature (changes in metabolic rate) and of CO2 added to the inspired air were studied. 2. Pulmonary ventilation increases when body temperature increases. The increase is brought about by an increase in respiratory frequency. No relationship is found between respiratory depth and temperature. 3. The rise in ventilation is provoked by the needs of metabolism and is not established for temperature regulating purposes (in the temperature interval 10°-35°C). 4. The ventilation per litre O2 consumed has a high numerical value (about 75, compared to about 20 in man). It varies with the body temperature and demonstrates that the inspired air is better utilized at the higher temperatures. 5. Pulmonary ventilation increases with increasing CO2 percentages in the inspired air between o and 3%. At further increases in the CO2 percentage (3-13.5%) it decreases again. 6. At each CO2 percentage the pulmonary ventilation reaches a steady state after some time (10-60 min.) and is then unchanged over prolonged periods (1 hr.). 7. The respiratory frequency in the steady state decreases with increasing CO2 percentages. The respiratory depth in the steady state increases with increasing CO2 percentages. This effect of CO2 breathing is not influenced by a change in body temperature from 20° to 30°C. 8. Respiration is periodically inhibited by CO2 percentages above 4%. This inhibition, causing a Cheyne-Stokes-like respiration, ceases after a certain time, proportional to the CO2 percentage (1 hr. at 8-13% CO2), and respiration becomes regular (steady state). Shift to room air breathing causes an instantaneous increase in frequency to well above the normal value followed by a gradual decrease to normal values. 9. The nature of the CO2 effect on respiratory frequency and respiratory depth is discussed, considering both chemoreceptor and humoral mechanisms.

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