Abstract:
The first application of gas chromatography
mass spectrometry (GC–MS) metabolomics to the analysis
of organic acid profiles in sera of asymptomatic
human immunodeficiency virus (HIV)-infected individuals
(n = 18) compared to uninfected controls (n = 21), is
reported here. Several organic acids are well-established
diagnostic biomarkers of mitochondrial dysfunction, making
the analysis of the organic acid metabolome well suited
to monitoring the progressive disruption of mitochondrial
structure and function during HIV infection. Using a
multifaceted analytical-bioinformatics procedure, at least
10 of these metabolites could be linked to (1) disrupted
mitochondrial metabolism, (2) changes in lipid metabolism
and (3) oxidative stress, all of which are aberrations caused
by HIV infection. Because of the role of the mitochondria
in apoptosis, higher levels of this type of cell death in
infected (compared to uninfected) individuals was used to
support GC–MS data. This study demonstrates that mass
spectrometry metabolomics detects biomarkers of mitochondrial
dysfunction which could potentially be developed
into indicators of HIV infection, perhaps also to
monitor disease progression and the response to antiretroviral
treatment.
