Uptaken aluminium accumulates in mitochondria

Abstract

Aluminium is a toxic element and a suspected human carcinogen. Despite this, being highly versatile, currently not classified as a carcinogenic, mutagenic and reprotoxic (CMR) chemical, and widely used, it is absorbed daily from a variety of products. Absorbed aluminium circulates systemically mainly via Transferrin (TF) and accumulates in human organs. Cellular incorporation of aluminium has been unequivocally demonstrated, but the subcellular localisation of the internalised metal requires clarification. Aluminium was previously shown to predominantly accumulate in granular-reticular organelles mainly concentrated in the perinuclear compartment. In this study we investigated the identity of these organelles. To this purpose, we developed a protocol to combine Lumogallion staining, which detects aluminium, with organelle-specific immunofluorescence. In MCF10A human mammary epithelial cells exposed to AlCl₃ for 3 h, aluminium does not co-localise with Calreticulin, a marker of the Endoplasmic Reticulum (ER) - an organelle that forms a network contiguous with the nuclear membrane - thus suggesting that the ER is not the primary site of aluminium accumulation. Neither does aluminium co-localises with TF receptor 1 (TFR1), thus making the involvement of endosomes in the process of aluminium internalisation unlikely. In contrast, in both human and murine mammary epithelial cells, aluminium specific Lumogallion fluorescence tightly co-localises with the fluorescence emitted by the mitochondrial probe MitoTracker in the perinuclear area. Our results provide strong experimental evidence that upon cellular uptake, aluminium accumulates in the mammalian mitochondrion.