Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Redox Equivalents and Mitochondrial Bioenergetics.

ABSTRACT: Mitochondrial energy metabolism depends upon high-flux and low-flux electron transfer pathways. The former provide the energy to support chemiosmotic coupling for oxidative phosphorylation. The latter provide mechanisms for signaling and control of mitochondrial functions. Few practical methods are available to measure rates of individual mitochondrial electron transfer reactions; however, a number of approaches are available to measure steady-state redox potentials (E h) of donor/acceptor couples, and these can be used to gain insight into rate controlling reactions as well as mitochondrial bioenergetics. Redox changes within the respiratory electron transfer pathway are quantified by optical spectroscopy and measurement of changes in autofluorescence. Low-flux pathways involving thiol/disulfide redox couples are measured by redox Western blot and mass spectrometry-based redox proteomics. Together, the approaches provide the opportunity to develop integrated systems biology descriptions of mitochondrial redox signaling and control mechanisms.

SUBMITTER: Roede JR

PROVIDER: S-EPMC6986360 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Redox Equivalents and Mitochondrial Bioenergetics.

Roede James R JR Go Young-Mi YM Jones Dean P DP

Methods in molecular biology (Clifton, N.J.) 20180101

Mitochondrial energy metabolism depends upon high-flux and low-flux electron transfer pathways. The former provide the energy to support chemiosmotic coupling for oxidative phosphorylation. The latter provide mechanisms for signaling and control of mitochondrial functions. Few practical methods are available to measure rates of individual mitochondrial electron transfer reactions; however, a number of approaches are available to measure steady-state redox potentials (E <sub>h</sub>) of donor/acc ...[more]

PMID: 29851002

Similar Datasets

Linking mitochondrial bioenergetics to insulin resistance via redox biology.

Project description:Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H(2)O(2)) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal that ultimately decreases insulin sensitivity. H(2)O(2) is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight into how H(2)O(2) emission may be linked via redox biology to the etiology of insulin resistance.

| S-EPMC3313496 | biostudies-literature

Hydrogen sulfide blocks HIV rebound by maintaining mitochondrial bioenergetics and redox homeostasis.

Project description:A fundamental challenge in human immunodeficiency virus (HIV) eradication is to understand how the virus establishes latency, maintains stable cellular reservoirs, and promotes rebound upon interruption of antiretroviral therapy (ART). Here, we discovered an unexpected role of the ubiquitous gasotransmitter hydrogen sulfide (H2S) in HIV latency and reactivation. We show that reactivation of HIV is associated with downregulation of the key H2S producing enzyme cystathionine-γ-lyase (CTH) and reduction in endogenous H2S. Genetic silencing of CTH disrupts redox homeostasis, impairs mitochondrial function, and remodels the transcriptome of latent cells to trigger HIV reactivation. Chemical complementation of CTH activity using a slow-releasing H2S donor, GYY4137, suppressed HIV reactivation and diminished virus replication. Mechanistically, GYY4137 blocked HIV reactivation by inducing the Keap1-Nrf2 pathway, inhibiting NF-κB, and recruiting the epigenetic silencer, YY1, to the HIV promoter. In latently infected CD4+ T cells from ART-suppressed human subjects, GYY4137 in combination with ART prevented viral rebound and improved mitochondrial bioenergetics. Moreover, prolonged exposure to GYY4137 exhibited no adverse influence on proviral content or CD4+ T cell subsets, indicating that diminished viral rebound is due to a loss of transcription rather than a selective loss of infected cells. In summary, this work provides mechanistic insight into H2S-mediated suppression of viral rebound and suggests exploration of H2S donors to maintain HIV in a latent form.

| S-EPMC8660018 | biostudies-literature

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics.

Project description:Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

| S-EPMC8466850 | biostudies-literature

Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover.

Project description:Bnip3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a mitochondrial BH3-only protein that contributes to cell death through activation of the mitochondrial pathway of apoptosis. Bnip3 is also known to induce autophagy, but the functional role of autophagy is unclear. In this study, we investigated the relationship between mitochondrial dysfunction and upregulation of autophagy in response to Bnip3 in cells lacking Bax and Bak. We found that Bnip3 induced mitochondrial autophagy in the absence of mitochondrial membrane permeabilization and Bax/Bak. Also, co-immunoprecipitation experiments showed that Bnip3 interacted with the autophagy protein LC3 (microtubule-associated protein light chain 3). Although Bax-/Bak-deficient cells were resistant to Bnip3-mediated cell death, inhibition of mitochondrial autophagy induced necrotic cell death. When investigating why these mitochondria had to be removed by autophagy, we discovered that Bnip3 reduced both nuclear- and mitochondria-encoded proteins involved in oxidative phosphorylation. Interestingly, Bnip3 had no effect on other mitochondrial proteins, such as Tom20 and MnSOD, or actin and tubulin in the cytosol. Bnip3 did not seem to reduce transcription or translation of these proteins. However, we found that Bnip3 caused an increase in mitochondrial protease activity, suggesting that Bnip3 might promote degradation of proteins in the mitochondria. Thus, Bnip3-mediated impairment of mitochondrial respiration induces mitochondrial turnover by activating mitochondrial autophagy.

| S-EPMC3058880 | biostudies-literature

ETHE1 and MOCS1 deficiencies: Disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts.

Project description:Ethylmalonic encephalopathy protein 1 (ETHE1) and molybdenum cofactor (MoCo) deficiencies are hereditary disorders that affect the catabolism of sulfur-containing amino acids. ETHE1 deficiency is caused by mutations in the ETHE1 gene, while MoCo deficiency is due to mutations in one of three genes involved in MoCo biosynthesis (MOCS1, MOCS2 and GPHN). Patients with both disorders exhibit abnormalities of the mitochondrial respiratory chain, among other biochemical findings. However, the pathophysiology of the defects has not been elucidated. To characterize cellular derangements, mitochondrial bioenergetics, dynamics, endoplasmic reticulum (ER)-mitochondria communication, superoxide production and apoptosis were evaluated in fibroblasts from four patients with ETHE1 deficiency and one with MOCS1 deficiency. The effect of JP4-039, a promising mitochondrial-targeted antioxidant, was also tested on cells. Our data show that mitochondrial respiration was decreased in all patient cell lines. ATP depletion and increased mitochondrial mass was identified in the same cells, while variable alterations in mitochondrial fusion and fission were seen. High superoxide levels were found in all cells and were decreased by treatment with JP4-039, while the respiratory chain activity was increased by this antioxidant in cells in which it was impaired. The content of VDAC1 and IP3R, proteins involved in ER-mitochondria communication, was decreased, while DDIT3, a marker of ER stress, and apoptosis were increased in all cell lines. These data demonstrate that previously unrecognized broad disturbances of cellular function are involved in the pathophysiology of ETHE1 and MOCS1 deficiencies, and that reduction of mitochondrial superoxide by JP4-039 is a promising strategy for adjuvant therapy of these disorders.

| S-EPMC6718683 | biostudies-literature

ATP13A2 regulates mitochondrial bioenergetics through macroautophagy.

Project description:Mitochondrial dysfunction and autophagy are centrally implicated in Parkinson's disease (PD). Mutations in ATP13A2, which encodes a lysosomal P-type ATPase of unknown function, cause a rare, autosomal recessive parkinsonian syndrome. Lysosomes are essential for autophagy, and autophagic clearance of dysfunctional mitochondria represents an important element of mitochondrial quality control. In this study, we tested the hypothesis that loss of ATP13A2 function will affect mitochondrial function. Knockdown of ATP13A2 led to an increase in mitochondrial mass in primary mouse cortical neurons and in SH-SY5Y cells forced into mitochondrial dependence. ATP13A2-deficient cells exhibited increased oxygen consumption without a significant change in steady-state levels of ATP. Mitochondria in knockdown cells exhibited increased fragmentation and increased production of reactive oxygen species (ROS). Basal levels of the autophagosome marker LC3-II were not significantly changed, however, ATP13A2 knockdown cells exhibited decreased autophagic flux, associated with increased levels of phospho-mTOR, and resistance to autophagy induction by rapamycin. The effects of ATP13A2 siRNA on oxygen consumption, mitochondrial mass and ROS production could be mimicked by inhibiting autophagy induction using siRNA to Atg7. We propose that decreased autophagy associated with ATP13A2 deficiency affects mitochondrial quality control, resulting in increased ROS production. These data are the first to implicate loss of ATP13A2 function in mitochondrial maintenance and oxidative stress, lending further support to converging genetic and environmental evidence for mitochondrial dysregulation in PD pathogenesis.

| S-EPMC3291101 | biostudies-literature

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders.

Project description:Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue's mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

| S-EPMC8473347 | biostudies-literature

Mitochondrial Bioenergetics and Dynamics in Secretion Processes.

Project description:Secretion is an energy consuming process that plays a relevant role in cell communication and adaptation to the environment. Among others, endocrine cells producing hormones, immune cells producing cytokines or antibodies, neurons releasing neurotransmitters at synapsis, and more recently acknowledged, senescent cells synthesizing and secreting multiple cytokines, growth factors and proteases, require energy to successfully accomplish the different stages of the secretion process. Calcium ions (Ca2+) act as second messengers regulating secretion in many of these cases. In this setting, mitochondria appear as key players providing ATP by oxidative phosphorylation, buffering Ca2+ concentrations and acting as structural platforms. These tasks also require the concerted actions of the mitochondrial dynamics machinery. These proteins mediate mitochondrial fusion and fission, and are also required for transport and tethering of mitochondria to cellular organelles where the different steps of the secretion process take place. Herein we present a brief overview of mitochondrial energy metabolism, mitochondrial dynamics, and the different steps of the secretion processes, along with evidence of the interaction between these pathways. We also analyze the role of mitochondria in secretion by different cell types in physiological and pathological settings.

| S-EPMC7256191 | biostudies-literature

Bioenergetics Consequences of Mitochondrial Transplantation in Cardiomyocytes.

Project description:Background Mitochondrial transplantation has been recently explored for treatment of very ill cardiac patients. However, little is known about the intracellular consequences of mitochondrial transplantation. This study aims to assess the bioenergetics consequences of mitochondrial transplantation into normal cardiomyocytes in the short and long term. Methods and Results We first established the feasibility of autologous, non-autologous, and interspecies mitochondrial transplantation. Then we quantitated the bioenergetics consequences of non-autologous mitochondrial transplantation into cardiomyocytes up to 28 days using a Seahorse Extracellular Flux Analyzer. Compared with the control, we observed a statistically significant improvement in basal respiration and ATP production 2-day post-transplantation, accompanied by an increase in maximal respiration and spare respiratory capacity, although not statistically significantly. However, these initial improvements were short-lived and the bioenergetics advantages return to the baseline level in subsequent time points. Conclusions This study, for the first time, shows that transplantation of non-autologous mitochondria from healthy skeletal muscle cells into normal cardiomyocytes leads to short-term improvement of bioenergetics indicating "supercharged" state. However, over time these improved effects disappear, which suggests transplantation of mitochondria may have a potential application in settings where there is an acute stress.

| S-EPMC7428632 | biostudies-literature

Modeling mitochondrial bioenergetics with integrated volume dynamics.

Project description:Mathematical models of mitochondrial bioenergetics provide powerful analytical tools to help interpret experimental data and facilitate experimental design for elucidating the supporting biochemical and physical processes. As a next step towards constructing a complete physiologically faithful mitochondrial bioenergetics model, a mathematical model was developed targeting the cardiac mitochondrial bioenergetic based upon previous efforts, and corroborated using both transient and steady state data. The model consists of several modified rate functions of mitochondrial bioenergetics, integrated calcium dynamics and a detailed description of the K(+)-cycle and its effect on mitochondrial bioenergetics and matrix volume regulation. Model simulations were used to fit 42 adjustable parameters to four independent experimental data sets consisting of 32 data curves. During the model development, a certain network topology had to be in place and some assumptions about uncertain or unobserved experimental factors and conditions were explicitly constrained in order to faithfully reproduce all the data sets. These realizations are discussed, and their necessity helps contribute to the collective understanding of the mitochondrial bioenergetics.

| S-EPMC2793388 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data