Theorizing on Mitochondria and Iron Homeostasis in Aging

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Here researchers theorize on connections between some measurable aspects of aging, those being mitochondrial damage and the role of iron in metabolic processes. As is always the case this sort of search for connections is bedeviled by the fact that aging is a global process: all sorts of changes happen in parallel, and establishing cause and effect, or even just linkage rather than mere association, is ever a challenge.

Free (labile or chelatable) iron is extremely redox-active and only represents a small fraction of the total mitochondrial iron population. Several studies have shown that the proportion of free iron increases with age, leading to increased Fenton chemistry in later life. It is not clear why free iron accumulates in mitochondria, but it does so in parallel with an inability to degrade and recycle damaged proteins that causes loss of mitochondrial protein homeostasis (proteostasis). The increase in oxidative damage that has been shown to occur with age might be explained by these two processes.
While this accumulation of oxidative damage has often been cited as causative to ageing there are examples of model organisms that possess high levels of oxidative damage throughout their lives with no effect on lifespan. Interestingly, these same animals are characterised by an outstanding ability to maintain correct proteostasis during their entire life. Reactive oxygen species can damage critical components of the iron homeostasis machinery, while the efficacy of mitochondrial quality control mechanisms will determine how detrimental that damage is.

Here we review the interplay between iron and organellar quality control in mitochondrial dysfunction and we suggest that a decline in mitochondrial proteostasis with age leaves iron homeostasis (where several key stages are thought to be dependent on proteostasis machinery) vulnerable to oxidative damage and other age-related stress factors. This will have severe consequences for the electron transport chain and TCA cycle (among other processes) where several components are acutely dependent on correct assembly, insertion and maintenance of iron-sulphur clusters, leading to energetic crisis and death.

Link: http://dx.doi.org/10.1016/j.exger.2013.12.015