MitoCom Tyrol
Summary
Concept
A physically active and nutritionally healthy life style induces regulatory mechanisms that maintain aerobic performance and support functional mitochondrial competence. Even in advancing age, exercise increases aerobic fitness and maintains muscle mitochondrial density above the sedentary benchmark, contributing to the high quality of life characteristic of alpine regions such as Tyrol. Functional mitochondrial competence and aerobic fitness reduce several age-related health risks, including cardiovascular and degenerative diseases, such as type 2 diabetes, neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s), and several types of cancer. As a result of a sedentary life style and progression to obesity, the decline of muscle mitochondrial capacity may contribute to accelerated ageing processes and development of degenerative diseases. Diagnostic evaluation of functional mitochondrial competence requires scientific and technological mitochondrial competence. Mitochondrial Competence Tyrol (MitoCom Tyrol – Sport and Healthcare) will combine the specialized scientific focus on mitochondrial research and exercise testing with the expertise of local companies of world-wide leadership in this expanding field. Beyond the added value emanating from the combination and coordination of these diagnostic elements, the consortium will collaborate on the implementation of refined and novel diagnostic protocols as a milestone towards an internationally recognized centre of excellence, with an explicit focus on sport and clinical perspectives to address mitochondrial health and disease.
Objectives
MitoCom Tyrol combines the expertise of experienced partners in a unique corporate framework. MitoCom Tyrol will establish a research and diagnostic laboratory network to form a Centre of Excellence in Mitochondrial Physiology, Pathology, Comprehensive Exercise Testing, and Genetic Fingerprinting. Diagnostic analyses include cardiopulmonary (VO2max; CPX) and metabolic (31P-NMR; Ergospect) exercise testing, evaluation of mitochondrial performance (high-resolution respirometry; OROBOROS INSTRUMENTS), and genetic screening (mtDNA haplotypes, relevant nuclear encoded genes). Refined state-of-the-art diagnostic protocols are extended and evaluated in a training programme under acute high-altitude hypoxia versus normoxic conditions with healthy control subjects. Exposure to acute hypoxia represents a typical condition for millions of individuals annually skiing or mountaineering in Austria and particularly in Tyrol. Comprehensive mitochondrial and exercise testing protocols will be developed and validated in these studies. Case studies will translate the scientific expertise into the clinical setting. As a result, MitoCom Tyrol will offer and apply these diagnostic services (product) for (i) monitoring of training programmes in competitive athletes, (ii) life style analyses of the general population, (iii) exercise interventions for preventive and therapeutic medicine, and (iv) clinical diagnosis of individual patients.
Technological and Scientific Innovation
Diagnosis of mitochondrial function has advanced to a new technological level by the introduction of high-resolution respirometry, and on a scientific level of innovation by multiple substrate-uncoupler-inhibitor titration protocols with permeabilized fibres from small muscle biopsies. Nevertheless, compared to the small needle biopsy, functional mt-diagnosis on far less invasive blood samples (thrombocytes) might provide a new perspective for large-scale screening of individual athletes, extended cohorts in clinical studies, and application for individual patients. Simultaneous measurement of mitochondrial respiration and additional parameters (mt-membrane potential by ion selective electrodes, hydrogen peroxide production by spectrofluorimetry coupled to the O2k) requires the development of new diagnostic protocols that can be applied to permeabilized muscle fibres and/or intact and permeabilized thrombocytes. Although conventional cardiopulmonary exercise testing (CPX) provides insights into the coupling of external to cellular respiration, it mirrors insufficiently the metabolic processes in the contracting and recovering muscle. Thus, combining CPX and techniques assessing bioenergetic processes in the working muscles will undoubtedly increase the conclusiveness of exercise testing in athletes and patients. These diagnostic MultiSensor protocols in combination with comprehensive exercise testing and genetic fingerprinting will generate an innovative repertoire of diagnostic tests that can be offered in the context of sports and mitochondrial diseases.
