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Talk:Mitochondrial Diagnostics

From Bioblast

Bioblast 2022



Talk:Mitochondrial Diagnostics

https://www.mitochondrial-diagnostics.com

Bioenergetic snapshots

The medical community and society in general are becoming increasingly aware of the central role of mitochondria in pharmacology, diseases, and healthy aging. In contrast to genetic mitochondrial screening ('genomic fingerprints'), functional mitochondrial diagnostics ('bioenergetic snapshots') has been largely neglected so far in clinical trials: diagnostic services remain limited and must be established for the support of large- and small-scale projects and pilot studies. The required 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]. Bioenergetic snapshots reflect the Evolutionary-genetic background, Age, Gender and sex, Lifestyle, and Environmental, pharmacological, and toxicological exposure (MitoEAGLE).

Mitochondrial Diagnostics

  • Mitochondrial Diagnostics builds upon the concept of standardized functional analyses and interpretation of bioenergetic snapshots of (1) cryopreserved PBMCs obtained from minimally invasive blood samples, (2) established cell cultures subjected to pharmacological screening, and (3) mitochondrial preparations obtained from animal or human tissue samples [3,4].
  • Mitochondrial Diagnostics aims at establishing laboratories for mitochondrial respiratory diagnostics offering bioenergetic snapshots in collaboration with academic and clinical partners, interest groups, funding agencies, and investors.
  • Bioenergetic snapshots are obtained from substrate-uncoupler-inhibitor titration protocols in respirometric assays interrogating specific mitochondrial functions [4]. Depending on the diagnostic focus, optimized mitochondrial preparations are applied covering the entire spectrum from living or permeabilized cells to mitochondria isolated from cultured cells or tissues.

Mitochondrial Diagnostics - tightly linked to innovative research

Standardized respirometric assays are supported by DatLab SUIT protocols. These can be selected according to targeted diagnostic profiles with the SUITbrowser. DatLab SUIT protocols provide real-time step-by-step guidelines to the experimenter and are matched by data analysis templates.
Respirometric protocols are extended by multisensor protocols including simultaneous monitoring of e.g. coenzyme Q redox state, NAD+/NADH (N) redox state, mitochondrial membrane potential, Ca2+ uptake capacity, H2O2 production and oxygen kinetics. In-depth bioenergetic studies may be considered complementary to diagnostic respirometric screening, linked to research projects aimed at resolving fundamental questions as a basis for developing new diagnostic standards.

Reproducibility, training, proficiency testing

The soon to be established enterprise Oroboros Diagnostics provides services for training and proficiency testing ranging from online coaching and on-site events, to interlaboratory ring tests. As such, Oroboros Diagnostics-Europe and Oroboros Diagnostics-US are of interest to O2k-Network laboratories and clinical centers. Concepts are implemented which have been elaborated at conferences of the Mitochondrial Physiology Society, in consortia lead by Oroboros Instruments with academic partners, and international projects:

» K-Regio project MitoCom
» K-Regio project MitoFit
» European H2020 COST Action MitoEAGLE
» European H2020 SME Innovation project NextGen-O2k

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

Circular

Dear O2k-Network partners and MitoEAGLE participants:
We would like to invite you to give us feedback on the following questions:
  1. Is your institution interested in joining a network on ‘Mitochondrial Diagnostics’, with the aim to apply for upcoming calls for submission of related grant proposals?
  2. Do you see future requirements of your institution/laboratory for advanced training and proficiency testing in Mitochondrial Diagnostics - Bioenergetic Snapshots, with joint technical publications in Bioenergetics Communications? – Next steps beyond MitoEAGLE.
  3. Are you in contact with clinicians or stakeholders who are responsible for clinical trials which may require the services of Mitochondrial Diagnostics? Can you provide contacts with stakeholders or investors, who might be interested in the joint venture of Mitochondrial Diagnostics – in Europe, in the US, and worldwide?
  4. Are there mitochondrial specialists in your team, who are interested in part-time or full-time employment in the group of Mitochondrial Diagnostics Experts? Such opportunities are likely to arise step-by-step, from online training sessions to globally networking home-office positions, from on-site positions at Oroboros Diagnostics to establish national consortia.
Please consider joining the Bioblast 2022 conference for person-to-person discussions and a round table on Mitochondrial Diagnostics.
Many thanks in advance for your feedback, and looking forward to renewing many personal contacts at Bioblast 2022.
With kind regards,
Erich Gnaiger, PhD
Editor-in-chief: Bioenergetics Communications - https://www.bioenergetics-communications.org
Oroboros Instruments
Mitochondria and Cell Research
Schoepfstrasse 18, A-6020 Innsbruck, Austria
T +43 512 566796, F +43 512 566796 20
erich.gnaiger@oroboros.at | https://www.oroboros.at/

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