I'm Not Dead Yet in Metabolic Regulation

Dear Colleagues,

Since 2000, when the INDY gene (SLC13A5/NaCT) was originally discovered as a longevity gene in Drosophila, a broad variety of functional roles of the INDY protein have been described, in particular in energy metabolism. The regulation of metabolic processes by the INDY gene was revealed through studies in lower organisms such as Drosophila and C. elegans, as well as mammalian species, up to monkeys and humans. Reducing the expression of INDY in lower species extends their life span by a mechanism resembling caloric restriction. Although, in humans, INDY is mainly found in the liver, it is also expressed in other tissues such as the brain, testes, and the adrenal gland. In all animal species tested so far, a reduced INDY function shows a vast majority of beneficial effects on energy metabolism, such as protection from dietary and age-related metabolic diseases. In contrast, a very rare loss of function mutation in human causes severe epileptic disease. Based on loss-of-function data in mouse and humans, as well as pharmacological intervention by anti-sense and small molecule inhibitors, the fundamental role of INDY in metabolic regulation in the liver; neuronal function; and, most recently, blood pressure regulation will be discussed in this Special Issue. Furthermore, its potential as a therapeutic target for finding new human medicines will be debated.

Prof. Andreas Birkenfeld
Dr. Grit Zahn
Guest Editors

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