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May 22-23, 2019 | Rome, Italy
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
IMMUNOLOGY
AND CANCER THERAPY
2nd Global Summit on
Immunotherapy 2019 Immunology Case Reports | Volume 3
CITRATE EXPORT PATHWAY AND UPREGULATION OF SLC25A1 AND ACLY GENES IN EN-
DOTOXIN/CYTOKINE-INDUCED MACROPHAGES
Vittoria Infantino1, 2, Paolo Convertini 1, 2, Anna Santarsiero1 and Vito Iacobazzi2
1 University of Basilicata, Italy
2 University of Bari, Italy
In response to proinflammatory triggers, macrophages undergo metabolic shift to support the bioenerget-
ic and biosynthetic requirements of the cell. Metabolite level changes are largely due to a rewiring of the
Krebs cycle following immune cell stimulation. Activated macrophages show an altered Krebs cycle, one con-
sequence of which is the accumulation of citrate. In this context most of citrate is diverted from Krebs cycle and
channelled into the “citrate export pathway” consisting in the increase of the export of citrate into cytosol by
the mitochondrial citrate carrier (CIC)-encoded by the SLC25A1 gene-followed by its cleavage into acetyl-CoA
and oxaloacetate by ATP citrate lyase (ACLY). Citrate export is a consequence of SLC25A1 and ACLY genes
upregulation in LPS as well as in TNFα and IFNγ activated macrophages. Remarkably, TNFα and LPS exert their
effect via NF-kB sites located in SLC25A1 and ACLY gene promoters. STAT1 is responsible for IFNγ-induced
SLC25A1 and ACLY upregulation, as demonstrated by its binding to STAT responsive elements in both gene
promoters. What is the fate of exported citrate? Citrate-derived acetyl-CoA is used to synthesize PGE2 and ox-
aloacetate to produce NADPH needed for NO and ROS. SLC25A1 and ACLY gene silencing or inhibition of CIC or
ACLY by different synthetic and natural molecules results in reduction of NO, ROS and PGE2 levels suggesting
that the citrate pathway can be a new target to be addressed in inflammation.
Vittoria Infantino et al., Immunol Case Rep 2019, Volume 3
Vittoria Infantino has completed her PhD in Cell Biochemistry and Pharmacology in 2005 studying the transcriptional regulation
of the human mitochondrial carrier genes. Further she focused on the mitochondrial carrier gene regulation mechanisms as Post-
Doc in the laboratory of Prof. Iacobazzi, Bari. She moved to University of Basilicata in 2008 where she is now Research Scientist in
Cellular Biology. Currently, her research is focused on the “Relationship between gene regulation and metabolism in physiological
and pathological conditions, with particular interest in cancer and inflammatory diseases”. To deepen these topics, she performed
a stay at the Trinity College Dublin-Biomedical Science Institute- School of Biochemistry-laboratory of Professor Luke O’Neill. She
has 36 publications in peer reviewed international journals with H-index 19 and has been serving as an Editorial Board Member to
reputed Journals.
BIOGRAPHY