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World J Gastroenterol. Nov 14, 2013; 19(42): 7369-7373
Published online Nov 14, 2013. doi: 10.3748/wjg.v19.i42.7369
Intestinal acyl-CoA synthetase 5: Activation of long chain fatty acids and behind
Christina Klaus, Min Kyung Jeon, Elke Kaemmerer, Nikolaus Gassler
Christina Klaus, Min Kyung Jeon, Elke Kaemmerer, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
Author contributions: Klaus C and Gassler N designed and wrote the article; Jeon MK and Kaemmerer E critically reviewed the literature and made technical notes.
Correspondence to: Nikolaus Gassler, Professor, Institute of Pathology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany. ngassler@ukaachen.de
Telephone: +49-241-8088897 Fax: +49-241-8082439
Received: June 21, 2013
Revised: July 20, 2013
Accepted: September 29, 2013
Published online: November 14, 2013
Processing time: 149 Days and 16.5 Hours
Abstract

The intestinal mucosa is characterized by a high complexity in terms of structure and functions and allows for a controlled demarcation towards the gut lumen. On the one hand it is responsible for pulping and selective absorption of alimentary substances ensuring the immunological tolerance, on the other hand it prevents the penetration of micro-organisms as well as bacterial outgrowth. The continuous regeneration of surface epithelia along the crypt-villus-axis in the small intestine is crucial to assuring these various functions. The core phenomena of intestinal epithelia regeneration comprise cell proliferation, migration, differentiation, and apoptosis. These partly contrarily oriented processes are molecularly balanced through numerous interacting signaling pathways like Wnt/β-catenin, Notch and Hedgehog, and regulated by various modifying factors. One of these modifiers is acyl-CoA synthetase 5 (ACSL5). It plays a key role in de novo lipid synthesis, fatty acid degradation and membrane modifications, and regulates several intestinal processes, primarily through different variants of protein lipidation, e.g., palmitoylation. ACSL5 was shown to interact with proapoptotic molecules, and besides seems to inhibit proliferation along the crypt-villus-axis. Because of its proapoptotic and antiproliferative characteristics it could be of significant relevance for intestinal homeostasis, cellular disorder and tumor development.

Keywords: Acyl-CoA synthetase; Apoptosis; Carcinogenesis; Colorectal cancer; Intestinal homeostasis

Core tip: Acyl-CoA synthetase 5 (ACSL5) activates long-chain fatty acids by coenzyme A linkage and plays a key role in fatty acid metabolism. On the basis of its mitochondrial localization, ACSL5 forms an exceptional member among the acyl-CoA synthetase family. Although its various functions are not yet fully understood, ACSL5 seems to represent a modifier of cellular vitality along the crypt-villus-axis.