-
Experimental Neurology Sep 2015Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are...
Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial isolation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II. To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a bilateral decrease in complex I-driven respiration and an increase in complex II-driven respiration 24h after focal TBI. These alterations in convergent electron flow though both complex I and II-driven respiration resulted in significantly lower maximal coupled and uncoupled respiration in the ipsilateral tissue compared to the contralateral side, for all measures. Surprisingly, increases in complex II and complex IV activities were most pronounced in the contralateral side of the brain from the focal injury, and where oxidative phosphorylation was increased significantly compared to sham values. We conclude that 24h after focal TBI in the immature brain, there are significant alterations in cerebral mitochondrial bioenergetics, with pronounced increases in complex II and complex IV respiration in the contralateral hemisphere. These alterations in mitochondrial bioenergetics present multiple targets for therapeutic intervention to limit secondary brain injury and support recovery.
Topics: Animals; Brain; Brain Injuries; Cell Respiration; Cerebral Cortex; Citrate (si)-Synthase; Disease Models, Animal; Energy Metabolism; Female; Functional Laterality; Mitochondria; Multienzyme Complexes; Respiratory Transport; Swine
PubMed: 26028309
DOI: 10.1016/j.expneurol.2015.05.009 -
British Medical Journal Feb 1952
Topics: Cell Respiration; Diffusion; Respiration
PubMed: 14896177
DOI: No ID Found -
British Medical Journal May 1958
Topics: Cell Respiration; Respiration; Respiration, Artificial
PubMed: 13536484
DOI: No ID Found -
Canadian Medical Association Journal Feb 1959
Topics: Cell Respiration; Electricity; Respiration; Respiration, Artificial
PubMed: 13618826
DOI: No ID Found -
British Medical Journal Feb 1953
Topics: Cell Respiration; Humans; Respiration; Respiratory Physiological Phenomena
PubMed: 13009260
DOI: No ID Found -
British Medical Journal Aug 1955
Topics: Breath Holding; Cell Respiration; Humans; Respiration
PubMed: 13240132
DOI: No ID Found -
The Journal of Physiology May 1949
Topics: Cell Respiration; Respiration
PubMed: 18149783
DOI: No ID Found -
Canadian Medical Association Journal Jun 1958
Topics: Cell Respiration; Humans; Hyperventilation; Respiration
PubMed: 13536940
DOI: No ID Found -
MBio Oct 2019Respiration is a fundamental process that has to optimally respond to metabolic demand and environmental changes. We previously showed that nitrate respiration, crucial...
Respiration is a fundamental process that has to optimally respond to metabolic demand and environmental changes. We previously showed that nitrate respiration, crucial for gut colonization by enterobacteria, is controlled by polar clustering of the nitrate reductase increasing the electron flux through the complex. Here, we show that the formate dehydrogenase electron-donating complex, FdnGHI, also clusters at the cell poles under nitrate-respiring conditions. Its proximity to the nitrate reductase complex was confirmed by its identification in the interactome of the latter, which appears to be specific to the nitrate-respiring condition. Interestingly, we have identified a multiprotein complex dedicated to handle nitric oxide resulting from the enhanced activity of the electron transport chain terminated by nitrate reductase. We demonstrated that the cytoplasmic NADH-dependent nitrite reductase NirBD and the hybrid cluster protein Hcp are key contributors to regulation of the nitric oxide level during nitrate respiration. Thus, gathering of actors involved in respiration and NO homeostasis seems to be critical to balancing maximization of electron flux and the resulting toxicity. Most bacteria rely on the redox activity of respiratory complexes embedded in the cytoplasmic membrane to gain energy in the form of ATP and of an electrochemical gradient established across the membrane. Nevertheless, production of harmful and toxic nitric oxide by actively growing bacteria as either an intermediate or side-product of nitrate respiration challenges how homeostasis control is exerted. Here, we show that components of the nitrate electron transport chain are clustered, likely influencing the kinetics of the process. Nitric oxide production from this respiratory chain is controlled and handled through a multiprotein complex, including detoxifying systems. These findings point to an essential role of compartmentalization of respiratory components in bacterial cell growth.
Topics: Cell Membrane; Cell Respiration; Escherichia coli; Microscopy, Fluorescence; Nitrates; Nitric Oxide
PubMed: 31641084
DOI: 10.1128/mBio.01832-19 -
Annals of Botany Nov 2011Plant growth and respiration still has unresolved issues, examined here using a model. The aims of this work are to compare the model's predictions with McCree's...
Plant growth and respiration re-visited: maintenance respiration defined - it is an emergent property of, not a separate process within, the system - and why the respiration : photosynthesis ratio is conservative.
BACKGROUND AND AIMS
Plant growth and respiration still has unresolved issues, examined here using a model. The aims of this work are to compare the model's predictions with McCree's observation-based respiration equation which led to the 'growth respiration/maintenance respiration paradigm' (GMRP) - this is required to give the model credibility; to clarify the nature of maintenance respiration (MR) using a model which does not represent MR explicitly; and to examine algebraic and numerical predictions for the respiration:photosynthesis ratio.
METHODS
A two-state variable growth model is constructed, with structure and substrate, applicable on plant to ecosystem scales. Four processes are represented: photosynthesis, growth with growth respiration (GR), senescence giving a flux towards litter, and a recycling of some of this flux. There are four significant parameters: growth efficiency, rate constants for substrate utilization and structure senescence, and fraction of structure returned to the substrate pool.
KEY RESULTS
The model can simulate McCree's data on respiration, providing an alternative interpretation to the GMRP. The model's parameters are related to parameters used in this paradigm. MR is defined and calculated in terms of the model's parameters in two ways: first during exponential growth at zero growth rate; and secondly at equilibrium. The approaches concur. The equilibrium respiration:photosynthesis ratio has the value of 0·4, depending only on growth efficiency and recycling fraction.
CONCLUSIONS
McCree's equation is an approximation that the model can describe; it is mistaken to interpret his second coefficient as a maintenance requirement. An MR rate is defined and extracted algebraically from the model. MR as a specific process is not required and may be replaced with an approach from which an MR rate emerges. The model suggests that the respiration:photosynthesis ratio is conservative because it depends on two parameters only whose values are likely to be similar across ecosystems.
Topics: Cell Respiration; Models, Biological; Photosynthesis; Plant Development; Plant Leaves; Plants
PubMed: 21948663
DOI: 10.1093/aob/mcr238