Mitochondrial Diagnostics

2022

Mitochondrial Diagnostics

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, functional mitochondrial diagnostics has been largely neglected so far in clinical trials: diagnostic services remain limited 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].

Oroboros Diagnostics - instrumental innovation to diagnostic standard

‘Oroboros Diagnostics’ aims at establishing Mitochondrial Diagnostics Centers in collaboration with academic partners, funding agencies, and investors. ‘Oroboros Diagnostics’ builds upon the concept of standardized functional analyses and interpretation [3,4] of the bioenergetic fingerprint 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.

Bioenergetic fingerprints are obtained from substrate-uncoupler-inhibitor titration protocols in respirometric assays interrogating specific mitochondrial functions [4]. These simple assays are extended by multisensor protocols including simultaneous monitoring of e.g. coenzyme Q redox state, NAD+/NADH (N) redox state, mitochondrial membrane potential, Ca²⁺ retention capacity, H₂O₂ production and oxygen kinetics. 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.

Reproducibility, training, proficiency testing

‘Oroboros Diagnostics’ provides services for training and proficiency testing ranging from online coaching, on-site events, to interlaboratory ring tests. As such, ‘Oroboros Diagnostics-Europe’ and ‘Oroboros Diagnostics-US’ is 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

Zdrazilova L, Hansikova H, Gnaiger E (2022) Comparable respiratory activity in attached and suspended human fibroblasts. PLoS ONE 17:e0264496.
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.
Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.8. https://doi.org/10.26124/mitofit:2021-0008
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:

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?
Do you see future requirements of your institution/laboratory for advanced training and proficiency testing in Mitochondrial Diagnostics, with joint technical publications in Bioenergetics Communications? – Next steps beyond MitoEAGLE.
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, worldwide?
Are 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 on-line training sessions to globally networking home-office positions, from on-site positions at Oroboros Diagnostics to establishing national consortia.

Please consider joining the Bioblast 2022 conference for person-to-person discussions and a round table on Mitochondrial Diagnostics.

May 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

Schöpfstrasse 18, A-6020 Innsbruck, Austria

T +43 512 566796, F +43 512 566796 20

[email protected] | https://www.oroboros.at/