Coupling of the polyamine and iron metabolism pathways in the regulation of proliferation: Mechanistic links to alterations in key polyamine biosynthetic and catabolic enzymes

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Darius J R LaneDes R Richardson

Abstract

Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins. Seven of these were regulated in a conserved manner by iron-depletion across different cell-types, with four proteins being down-regulated (i.e., acireductone dioxygenase 1 [ADI1], methionine adenosyltransferase 2α [MAT2α], Antizyme and polyamine oxidase [PAOX]) and three proteins being up-regulated (i.e., S-adenosyl methionine decarboxylase [AMD1], Antizyme inhibitor 1 [AZIN1] and spermidine/spermine-N1-acetyltransferase 1 [SAT1]). Depletion of iron also markedly decreased polyamine pools (i.e., spermidine and/or spermine, but not putrescine). Accordingly, iron-depletion also decreased S-adenosylmethionine that is essential for spermidine/spermine biosynthesis. Iron-depletion additionally reduced 3H-spermid...Continue Reading

Citations

Jun 6, 2018·Journal of Alzheimer's Disease : JAD·Darius J R LaneAshley I Bush
Oct 12, 2018·Medical Sciences : Open Access Journal·Bruno Ramos-MolinaRafael Peñafiel
Feb 23, 2020·Biotechnology Letters·Berta Capella RocaMartin Clynes
Nov 2, 2019·Antioxidants & Redox Signaling·Dong-Hun BaeDes R Richardson
Jan 9, 2019·Frontiers in Microbiology·Mareike BergesDieter Jahn
Aug 7, 2020·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Ola Ibrahim, Jeff O'Sullivan
Aug 14, 2021·Trends in Biochemical Sciences·Francesca RizzolloPatrizia Agostinis

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