Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome.
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.
Department of Pharmacy, University of Pisa, Pisa, Italy.
F
F
Ciregia
Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund, Germany.
L
L
Kollipara
Department of Pharmacy, University of Pisa, Pisa, Italy.
L
L
Giusti
Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund, Germany.
R P
RP
Zahedi
Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
C
C
Giacomelli
Department of Pharmacy, University of Pisa, Pisa, Italy.
M R
MR
Mazzoni
Department of Pharmacy, University of Pisa, Pisa, Italy.
G
G
Giannaccini
Division of Psychiatry, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
P
P
Scarpellini
Istituto di Biochimica e Biochimica Clinica, Università Cattolica, Rome, Italy.|Proteomics and Metabonomics Unit, IRCCS-Fondazione Santa Lucia, Rome, Italy.
A
A
Urbani
Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund, Germany.|Department of Chemistry, College of Physical Sciences, University of Aberdeen. Aberdeen, UK.|Medizinische Fakultät, Medizinische Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
A
A
Sickmann
Department of Pharmacy, University of Pisa, Pisa, Italy.
A
A
Lucacchini
Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
L
L
Bazzichi
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