Effects of iron imbalances on mitochondrial activity and on the overall metabolism in vivo

Abstract

Introduction&Objectives Mitochondria are dynamic organelles, involved in different cellular functions, including oxidative phosphorylation, where iron is a fundamental co-factor [1]. Besides being central part of mitochondrial I-IV complexes in the electron transport system, iron also regulates the Krebs cycle by modulating mitochondrial aconitase [2, 3]. Hence, imbalances of iron homeostasis could affect mitochondrial activity and cellular metabolism [4]. Nevertheless, little is known on that. Therefore, we aimed at investigating the impact of alterations of iron homeostasis on mitochondrial function, and on peripheral blood metabolites, in order to potentially identify distinctive signatures. Materials&Methods Mitochondrial function was studied in liver samples of 10-week old FVB mice and C57BL/6N mice, receiving either normal- or high iron (25 g/kg)-diet two weeks before being sacrificed. Livers were homogenized and mitochondrial respiration was assessed by means of high resolution respirometry (OROBOROS Instruments, Austria). Peripheral blood was collected, and metabolomics analysis was performed by using liquid chromatography-mass spectrometry (LC-MS). Results&Conclusion Our ongoing experiments indicate that dietary iron supplementation affects the phosphorylation system in the mouse liver of both FVB and C57BL/6N mice. The analysis of peripheral blood metabolites is currently under investigation, and might provide useful information on changes in the overall metabolism.