Gnaiger 2022 ESCI Bari

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Erich Gnaiger
Gnaiger E (2022) Bioenergetic cluster analysis – diagnostic evaluation of mitochondrial respiratory control in human fibroblasts. 56th Annual Scientific Meeting of the European Society for Clinical Investigation.

Link: 56th Annual Scientific Meeting of the European Society for Clinical Investigation

Gnaiger E (2022)

Event: ESCI 2022 Bari IT

The medical community and our society are becoming increasingly aware of the role of mitochondria in pharmacology, diseases, and healthy aging. In contrast, mitochondrial diagnostics remain largely neglected in clinical trials: diagnostic services fail to support large- and small-scale projects and pilot studies. Quality control ― necessary for clinical trials and highly deserved in any scientific study to ensure reproducibility [1] ― is hardly affordable in the typical research laboratory [2].

In a meta-analysis of human skin fibroblasts, high-resolution respirometry and polarography covering cell senescence and the human age range were compared with multiwell respirometry to evaluate published data on mitochondrial function in relation to clinical diagnostic standards [3]. The common coupling control protocol measures ROUTINE respiration of living cells followed by sequential titrations of oligomycin, uncoupler, and inhibitors of electron transfer [4].

Bioenergetic cluster analysis BCA increases the resolution of outliers. Isolinear clusters are separated by variations in quantities that correlate with rates, whereas heterolinear clusters fall on different regression lines. Dispersed clusters are separated by critical threshold values. BCA provides guidelines for establishing quality control for bioenergetic databases in mitochondrial physiology. The present example on human fibroblasts as models of diseases may serve as a reference for bioenergetic mitochondrial diagnostics complementary to genomic or proteomic standards.


Bioblast editor: Plangger M O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck MitoFit, AT Innsbruck Oroboros


Affiliations

Oroboros Instruments GmbH, Oroboros Ecosystem, Innsbruck, Austria.

References

  1. Zdrazilova L, Hansikova H, Gnaiger E (2022) Comparable respiratory activity in attached and suspended human fibroblasts. PLoS ONE 17:e0264496.
  2. Ioannidis JPA, Greenland S, Hlatky MA, Khoury MJ, Macleod MR, Moher D, Schulz KF, Tibshirani R (2014) Increasing value and reducing waste in research design, conduct, and analysis. Lancet 383:166-75.
  3. Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.8. https://doi.org/10.26124/mitofit:2021-0008
  4. Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002

List of abbreviations, terms and definitions - MitoPedia

» MitoPedia: Terms and abbreviations


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

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


Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k