Impact of Autophagy and Aging on Iron Load and Ferritin in Drosophila Brain.

Anne-Claire Jacomin,Kalotina Geraki,Vindy Tjendana-Tjhin,Ioannis P Nezis,Joanna F Collingwood,Jake Brooks

doi:10.3389/fcell.2019.00142

Anne-Claire Jacomin, Kalotina Geraki + Show 4 more

Open Access

https://doi.org/10.3389/fcell.2019.00142

Copy DOI

Abstract

Biometals such as iron, copper, potassium, and zinc are essential regulatory elements of several biological processes. The homeostasis of biometals is often affected in age-related pathologies. Notably, impaired iron metabolism has been linked to several neurodegenerative disorders. Autophagy, an intracellular degradative process dependent on the lysosomes, is involved in the regulation of ferritin and iron levels. Impaired autophagy has been associated with normal pathological aging, and neurodegeneration. Non-mammalian model organisms such as Drosophila have proven to be appropriate for the investigation of age-related pathologies. Here, we show that ferritin is expressed in adult Drosophila brain and that iron and holoferritin accumulate with aging. At whole-brain level we found no direct relationship between the accumulation of holoferritin and a deficit in autophagy in aged Drosophila brain. However, synchrotron X-ray spectromicroscopy revealed an additional spectral feature in the iron-richest region of autophagy-deficient fly brains, consistent with iron–sulfur. This potentially arises from iron–sulfur clusters associated with altered mitochondrial iron homeostasis.

Highlights

Iron is an essential biometal, widely used as a cofactor by a variety of proteins
We show that iron and holoferritin accumulate in the brain from old flies regardless of their autophagy status, suggesting that autophagy is not essential to regulate total iron levels in the Drosophila brain
Ferritin Is Expressed in Adult Drosophila Brain

Summary

Introduction

Iron is an essential biometal, widely used as a cofactor by a variety of proteins. Imbalance in iron metabolism, where either a deficiency or excess of iron may have harmful effects, and impaired iron metabolism may be modulators of neurodegeneration in several genetic or sporadic neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis (Ward et al, 2014; Angelova and Brown, 2015; Biasiotto et al, 2016).Ferritin is a universal iron storage protein. The heavy (H) and light (L) chains, assemble in different ratios into 24-subunit heteropolymers, in which iron can be stored in a mineralized form. Expression of both H and L ferritin chains are closely related to iron bioavailability (Gray and Hentze, 1994). Drosophila genome encodes two types of subunits, known as heavy-chain homolog (Fer1HCH) and light-chain homolog (Fer2LCH) (Georgieva et al, 2002; Nichol et al, 2002; Hamburger et al, 2005). A mitochondrial ferritin subunit was lately identified in both mammals and insects (Levi et al, 2001; Missirlis et al, 2006). On the contrary to other ferritins, mitochondrial ferritin assembles as homopolymers (Levi et al, 2001)

Methods

Results

Conclusion