Extracellular Citrate in Health and Disease.

Abstract:

:Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiological states; its decrease has been correlated with male infertility, brain diseases and metastatic cancer. In this review we discuss the role of citrate as an energy substrate for sperm. We also review the function of citrate released by astrocytes in the normal operation of neurons, and consequently we suggest a potential role of neuronal plasma membrane citrate transporters in mental disorders. Finally, we review recent relevant publications studying blood, urine and tissue citrate levels in cancer patients and hypothesize that extracellular citrate supports cancer cell metabolism critical for metastasis. Despite the importance of extracellular citrate in physiological and pathophysiological processes, surprisingly little is known about citrate synthesis in specialized cells, or about citrate transporters controlling citrate movement across various membranes. Determination of the molecular origin of citrate transporters in astrocytes, sperm and cancer cells could offer novel therapeutic targets and the possibility to pharmacologically regulate citrate release and uptake for preventing male infertility, treating mental diseases and targeting cancer.

journal_name

Curr Mol Med

authors

Mycielska ME,Milenkovic VM,Wetzel CH,Rümmele P,Geissler EK

doi

10.2174/1566524016666151123104855

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

884-91

issue

10

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-72039

journal_volume

15

pub_type

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