Cellular Bioenergetics

Bioenergetics ◽  
2013 ◽  
pp. 255-302 ◽  
Author(s):  
David G. Nicholls ◽  
Stuart J. Ferguson
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Øyvind Strømland ◽  
Juha P. Kallio ◽  
Annica Pschibul ◽  
Renate H. Skoge ◽  
Hulda M. Harðardóttir ◽  
...  

AbstractNicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 233
Author(s):  
Britta Trautwein ◽  
Tamara Merz ◽  
Nicole Denoix ◽  
Csaba Szabo ◽  
Enrico Calzia ◽  
...  

Genetic deletion of 3-mercaptopyruvate sulfurtransferase (MST) is known to result in hypertension and cardiac hypertrophy in older mice, and is associated with increased anxiety-like behaviors. Endogenous hydrogen sulfide (H2S) produced by MST in the mitochondria is also known to be involved in physiological and cellular bioenergetics, and its dysfunction associated with depressive behavior and increased cardiovascular morbidity. Interestingly, early life stress has been shown to lead to a significant loss of cystathionine-γ-lyase (CSE) and oxytocin receptor (OTR) expression in the heart. Thus, we were interested in testing the hypothesis of whether genetic MST mutation (ΔMST) would affect cardiac CSE and OTR expression and affect the mitochondrial respiration in a clinically relevant, resuscitated, mouse model of trauma and hemorrhagic shock. In ΔMST mice, we found a reduction of CSE and OTR in both the naive as well as injured state, in contrast to the wild type (wt) controls. Interestingly, the ΔMST showed a different complex IV response to injury than the wt controls, although our claims are based on the non-demonstrated assumption that naive wt and naive ΔMST mice have comparable complex IV activity. Finally, hemorrhagic shock led to a reduction of CSE and OTR, confirming previous results in the injured mouse heart. To date, the exact mechanisms of the cardiac interaction between H2S and OT are not clear, but they point the way to potential cardioprotective therapies.


2013 ◽  
Vol 85 (24) ◽  
pp. 11677-11680 ◽  
Author(s):  
Tesniem F. Shinawi ◽  
Danielle W. Kimmel ◽  
David E. Cliffel

1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.


2021 ◽  
Vol 42 ◽  
pp. 401-414
Author(s):  
C Voskamp ◽  
◽  
LA Anderson ◽  
WJLM Koevoet ◽  
S Barnhoorn ◽  
...  

Mesenchymal stem cells (MSCs) are promising cells for regenerative medicine therapies because they can differentiate towards multiple cell lineages. However, the occurrence of cellular senescence and the acquiring of the senescence-associated secretory phenotype (SASP) limit their clinical use. Since the transcription factor TWIST1 influences expansion of MSCs, its role in regulating cellular senescence was investigated. The present study demonstrated that silencing of TWIST1 in MSCs increased the occurrence of senescence, characterised by a SASP profile different from irradiation-induced senescent MSCs. Knowing that senescence alters cellular metabolism, cellular bioenergetics was monitored by using the Seahorse XF apparatus. Both TWIST1-silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption rate compared to control MSCs, while TWIST1-silencing-induced senescent MSCs had a low extracellular acidification rate compared to irradiation-induced senescent MSCs. Overall, data indicated how TWIST1 regulation influenced senescence in MSCs and that TWIST1 silencing-induced senescence was characterised by a specific SASP profile and metabolic state.


Author(s):  
Blanca I. Aldana ◽  
Claudia Salcedo ◽  
Kristine K. Freude ◽  
Helle S. Waagepetersen

2019 ◽  
Vol 401 (1) ◽  
pp. 3-29 ◽  
Author(s):  
Bradford G. Hill ◽  
Sruti Shiva ◽  
Scott Ballinger ◽  
Jianhua Zhang ◽  
Victor M. Darley-Usmar

AbstractIt is now becoming clear that human metabolism is extremely plastic and varies substantially between healthy individuals. Understanding the biochemistry that underlies this physiology will enable personalized clinical interventions related to metabolism. Mitochondrial quality control and the detailed mechanisms of mitochondrial energy generation are central to understanding susceptibility to pathologies associated with aging including cancer, cardiac and neurodegenerative diseases. A precision medicine approach is also needed to evaluate the impact of exercise or caloric restriction on health. In this review, we discuss how technical advances in assessing mitochondrial genetics, cellular bioenergetics and metabolomics offer new insights into developing metabolism-based clinical tests and metabolotherapies. We discuss informatics approaches, which can define the bioenergetic-metabolite interactome and how this can help define healthy energetics. We propose that a personalized medicine approach that integrates metabolism and bioenergetics with physiologic parameters is central for understanding the pathophysiology of diseases with a metabolic etiology. New approaches that measure energetics and metabolomics from cells isolated from human blood or tissues can be of diagnostic and prognostic value to precision medicine. This is particularly significant with the development of new metabolotherapies, such as mitochondrial transplantation, which could help treat complex metabolic diseases.


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