Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome.

F Ciregia,L Bazzichi,M R Mazzoni,P Scarpellini,R P Zahedi,G Giannaccini,L Kollipara,A Urbani,L Giusti,A Sickmann,C Giacomelli,A Lucacchini

doi:10.1038/tp.2016.184

Abstract

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins. Subsequently, we selected three proteins that were validated using western blot analysis in a big cohort of subjects (n=45 CFS; n=45 healthy), using whole saliva (WS). The selected proteins were as follows: aconitate hydratase (ACON), ATP synthase subunit beta (ATPB) and malate dehydrogenase (MDHM). Results for ATPB and ACON confirmed their upregulation in CFS. However, the MDHM alteration was not confirmed. Thereafter, seeing the great variability of clinical features of CFS patients, we decided to analyze the expression of our proteins after splitting patients according to clinical parameters. For each marker, the values were actually higher in the group of patients who had clinical features similar to the ill twin. In conclusion, these results suggest that our potential markers could be one of the criteria to be taken into account for helping in diagnosis. Furthermore, the identification of biomarkers present in particular subgroups of CFS patients may help in shedding light upon the complex entity of CFS. Moreover, it could help in developing tailored treatments.

Highlights

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest, that lasts longer than 6 months, and that may be aggravated by physical or mental activity
The discovery and validation of more objective markers could provide an important support for CFS diagnosis and therapy
As evidence suggests that CFS can be underpinned by mitochondrial dysfunctions, we analyzed mitochondrial proteins obtained from platelets

Summary

INTRODUCTION

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest, that lasts longer than 6 months, and that may be aggravated by physical or mental activity. The diagnosis of CFS remains a clinical endeavor and can be made after the exclusion of medical conditions that may explain the prolonged fatigue as well as a number of psychiatric diagnoses (for example, bipolar disorder, eating disorders, psychotic disorders and melancholic depression) This difficulty in defining CFS, due to the lack of diagnostic markers, complicates epidemiological studies. One of the most common proposed causative agent is a viral infection, and vaccines have been indicated to contribute to the development of CFS; data are controversial.[8,9,10,11,12] In addition, several immune abnormalities have been reported in CFS patients; many of the observed abnormalities were not confirmed by others, resulting in inconsistent findings across studies.[13,14] there is a clear need to enhance CFS understanding Another area of investigation is the likely connection of CFS with defective mitochondrial function.

Study design

Findings

DISCUSSION