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Gnaiger 2021 MitoFit BCA

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Gnaiger MitoFit Preprints 2020.4
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Gnaiger 2021 MitoFit BCA

Publications in the MiPMap
Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.#. doi:10.26124/mitofit:2021-000# (in preparation)

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MitoFit pdf

Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts

Gnaiger Erich (2021-##-##) MitoFit Preprints

Abstract: Cell respiration reflects mitochondrial fitness and plays a pivotal role in health and disease. Despite the rapidly increasing number of applications of cell respirometry to address current challenges in biomedical research, cross-references are rare between respirometric projects and platforms. Evaluation of accuracy and reproducibility between laboratories requires presentation of results in a common format independent of the applied method. When cell respiration is expressed as oxygen consumption rate in an experimental chamber, normalization is mandatory for comparability of results. Concept-driven normalization and regression analysis are key towards bioenergetic cluster analysis presented as a graphical tool to identify discrete data populations.

In a meta-analysis of human skin fibroblasts, high-resolution respirometry and polarography covering cell senescence and the human age range are compared with multiwell respirometry. The common coupling control protocol measures ROUTINE respiration of living cells followed by sequential titrations of oligomycin, uncoupler, and inhibitors of electron transfer.

Bioenergetic cluster analysis increases the resolution of outliers within and differences between groups. An outlier-skewness index is introduced as a guide towards logarithmic transformation for statistical analysis. Isolinear clusters are separated by variations in the extent of a quantity that correlates with the rate, whereas heterolinear clusters fall on different regression lines. Dispersed clusters are clouds of data separated by a critical threshold value. Bioenergetic cluster analysis provides new insights into mitochondrial respiratory control and a guideline for establishing a quality control paradigm for bioenergetics and databases in mitochondrial physiology. ‱ Keywords: human dermal fibroblasts HDF, living cells ce, cell respiration, coupling control, oxidative phosphorylation OXPHOS, age, senescence, bioenergetic cluster analysis BCA, meta-analysis, normalization, high-resolution respirometry HRR, Oroboros O2k, Seahorse XF Analyzer, outlier-skewness index OSI, regression analysis ‱ Bioblast editor: Gnaiger E ‱ O2k-Network Lab: AT Innsbruck Oroboros

ORCID: ORCID.png Gnaiger Erich

References

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2020
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MitoFit pdf
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2021
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2020
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Cited by

  • KomlĂłdi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. Bioenerg Commun 2021.3. https://doi.org/10.26124/bec:2021-0003

Keywords


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Support

Template NextGen-O2k.jpg
Supported by project NextGen-O2k which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 859770.


Labels: MiParea: Respiration, Instruments;methods  Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Fibroblast  Preparation: Intact cells 

Regulation: Coupling efficiency;uncoupling  Coupling state: LEAK, OXPHOS, ET  Pathway: ROX  HRR: Oxygraph-2k 

SUIT-003, MitoEAGLEPublication, MitoFit 2021 ace-sce, MitoFit 2021 Q 

Term Link to MitoPedia term Symbol Unit Links and comments
catabolic rate of respiration Cell respiration JkO2; IkO2 varies flux J versus flow I
catabolic reaction Cell respiration k -
cell count Count Nce [x] see number of cells; countable object s=ce
cell-count concentration Concentration Cce [x∙L­-1] Cce = Nce∙V-1; count concentration C versus amount concentration c; subscript ce indicates the entity type: concentration of ce. But it does not signal 'per entity', which would be written as 'per cell' Xce.
cell mass Body mass mce [kg] mass of cells m versus mass per cell (per single entity cell) MXce
cell mass, mass per cell Body mass MXce [kg∙x­-1] mass per single cell MXce; upper case M and subscript X signal 'per count', subscript ce signals the entity s=ce; in a context restricted to cells or molecules or a particular organism such as humans, the abbreviated symbol M [kg∙x­-1] provides a sufficiently informative signal, particularly in combination with the explicit unit.
cell-mass concentration in chamber Concentration Cmce [kg∙L­-1] see Cms: Cmce = mce∙V-1; upper case C alone would signal 'count concentration' (CN is more explicit), whereas the signal for 'mass concentration' is in the combination Cm.
concentration of O2, amount Concentration cO2 = nO2∙V­-1 [mol∙L­-1] [O2]
concentration of s, count Concentration Cs = Ns∙V­-1 [x∙L-1] (number concentration Cohen 2008 IUPAC Green Book); the signal for count concentration is given by the upper case C in contrast to c for amount concentration. In both cases, the subscript X indicates the entity type, not to be confused with a number of entities.
count of Xs Count Ns [x] SI; see number of entities Xs
coupling control Coupling-control ratio CCR -
coupling control state Coupling control state CCS -
electron transfer pathway Electron transfer pathway ET pathway -
electron transfer, state Electron transfer pathway ET - (State 3u)
electron transfer system Electron transfer pathway ETS - (electron transport chain)
elementary entity Entity Xs [x] single countable object of sample type s
ET capacity ET capacity E varies rate
flow, for O2 Flow IO2 [mol∙s-­1] system-related extensive quantity
flux, for O2 Flux JO2 varies size-specific quantity
flux control ratio Flux control ratio FCR 1 background/reference flux
International System of Units International System of Units SI - Cohen 2008 IUPAC Green Book
LEAK state LEAK respiration LEAK - (compare State 4)
LEAK respiration LEAK respiration L varies rate
living cells Living cells ce - (intact cells)
mass concentration of sample s in chamber Concentration Cms [kg∙L-1]
mass of sample s in a mixture Mass ms [kg] SI: mass of pure sample mS
mass per single object Body mass MNX [kg∙x­1] SI: m(X); compare molar mass M(X)
mitochondria or mitochondrial Mitochondria mt -
mitochondrial concentration Mitochondrial marker, Concentration CmtE = mtE∙V-1 [mtEU∙L-1]
mitochondrial content per X Mitochondrial marker mtENX [mtEU∙x­-1] mtENX = mtE∙NX-1
mitochondrial elementary marker Mitochondria mtE [mtEU] quantity of mt-marker
mitochondrial elementary unit Mitochondria mtEU varies specific units for mt-marker
MitoPedia MitoPedia, MitoPedia: Respiratory states
normalization of rate Normalization of rate - -
number of cells Count Nce [x] total cell count of living cells, Nce = Nvce + Ndce
oxidative phosphorylation Oxidative phosphorylation OXPHOS -
OXPHOS-capacity OXPHOS-capacity P varies rate
OXPHOS state OXPHOS-capacity OXPHOS - OXPHOS-state distinguished from the process OXPHOS (State 3 at kinetically-saturating [ADP] and [Pi])
oxygen concentration Oxygen concentration cO2 = nO2∙V­-1 [mol∙L­-1] [O2]
oxygen solubility Oxygen solubility SO2 [”mol·kPa-1]
oxygen flux, in reaction r Oxygen flux JrO2 varies
quantities, symbols, and units Quantities, symbols, and units - - An explanation of symbols and unit [x]
rate in ET state Electron transfer pathway E varies ET capacity
rate in LEAK state LEAK respiration L varies L(Omy)
rate in ROX state Residual oxygen consumption Rox varies
residual oxygen consumption Residual oxygen consumption ROX; Rox - state ROX; rate Rox
respiration Respirometry JrO2 varies rate of reaction r
respiratory state MitoPedia: Respiratory states - -
steay state Steady state - -
substrate-uncoupler-inhibitor-titration Substrate-uncoupler-inhibitor titration SUIT -
system System - -
unit elementary entity Entity UX [x] single countable object
uncoupling Uncoupler titrations - -
volume of experimental chamber Volume V [L] liquid volume V including the sample s