A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers for mitochondrial respiratory chain enzyme activities.

D Yubero,A Nascimento,R Artuch,C Jiménez-Mallebrera,L Gort,M M O’Callaghan,A García-Cazorla,A Ribes,C Jou,A Adin,R Montero,J Montoya,P Navas,M D Ugarte

doi:10.1038/s41598-016-0008-1

Abstract

Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.

Highlights

Mitochondrial disease diagnosis is a complex process that relies on clinical, biochemical, neuroimaging, histological, and molecular data
Coenzyme Q10 (CoQ) correlation coefficients with all the mitochondrial respiratory chain (MRC) enzyme activities were higher compared with those obtained between citrate synthase (CS) and the other MRC enzymes (Table 2)
When the CoQ concentrations and MRC enzyme activities were normalized to CS activity values, the highest correlation coefficient was observed between CoQ and complex II + III (Table 3)

Summary

Introduction

Mitochondrial disease diagnosis is a complex process that relies on clinical, biochemical, neuroimaging, histological, and molecular data. It has been suggested that total muscle CoQ is the best predictor of an MRC abnormality[12]. These findings strongly support the hypothesis that routine quantitative evaluation of muscle CoQ might be a new tool for both estimating MRC enzyme activities in muscle biopsies and diagnosing CoQ deficiency states[10, 12]. Correspondence and requests for materials should be addressed to R.A. Correspondence and requests for materials should be addressed to R.A With this background, our aim was to develop and apply an exploratory statistical procedure to assess muscle CoQ content and CS activity as biomarkers of mitochondrial activity evaluated by the analysis of MRC enzyme activities. After the initial statistical assessment, subpopulations of individuals displaying a high linear correlation coefficient among the different biochemical variables were identified

Objectives

Methods

Results

Conclusion