Is mtDNA copy number a good biomarker for predict cardiorespitatory fitness level?

Abstract

BACKGROUND. Mitochondrion is the cellular organelle that produces energy for the organism, generating adenosine triphosphate using O2 and nutrients. Physical capacity levels are thus directly related with mitochondrial activity (1). Mitochondrial DNA (mtDNA) copy number is proportional to the mtDNA volume in a cell, and can be used as a measure of mitochondrial function (2). The aim of this study was to evaluate the possible relationship between cardiorespiratory fitness level and leukocyte relative mtDNA copy number in healthy men. METHODS. 103 healthy men aged between 18-45 divided into two groups: high cardiorespiratory fitness level with VO2max above 55 ml.kg-1.min-1 (Group 1) and low cardiorespiratory fitness level with VO2max below 45 ml.kg-1.min-1 (Group 2). VO2max was measured in a maximal incremental treadmill test a with gas analyser (ULTIMA series, MEDGRAPHICS, cardiorespiratory diagnostic). mtDNA copy number was measured in peripheral blood leukocytes. Blood samples were collected in collection tubes containing EDTA and DNA extraction was obtained using the High Pure PCR Template Preparation Kit. The leukocyte relative mtDNA copy number was analysed using a real-time polymerase chain reaction (RT-PCR) method with SYBR Green. Threshold cycle number (Ct) values of the β-globin nuclear gene and the COX1 mitochondrial gene were used to determine the mtDNA content. The content of the mtDNA was calculated using the following equation: relative copy number = 2ΔCt (ΔCt = Ct nDNA - Ct mitDNA). For statistical analyses, we used the U the Mann-Whitney test with software SPSS for Windows version 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS. VO2max was 58.7±3.9 ml.kg-1.min-1 for group 1 and 39.6±3.8 ml.kg-1.min-1 for group 2. We found significant differences in mtDNA copy number between the groups (392.18 ± 881.2 for group 1 and 156.41 ± 154.3 for group 2) (p=0,044). DISCUSSION. Our results are in accorance to Chang et al. 2016 results in postmenopausal women (3) and to Bayarca et al. 2016 results in athletes (4). In conclusion, it seems that mtDNA copy number can represent an interesting novel biomarker for cardiorespiratory fitness capacity level. Practical implementation: mtDNA copy number is a good indirect predictor of mitochondrial function and usefull for mesure mitochondrial biogenesis in physical activity.