Endocytic iron trafficking and mitochondria in Parkinson's disease

Abstract

Parkinson's disease (PD) - the second most common neurodegenerative disorder - is a multifactorial disease, the causes of which should be sought in complex and detrimental interactions between genetic and environmental factors. Multiple lines of evidence, however, identify mitochondrial dysfunction, oxidative stress, and iron accumulation as central pathogenic mechanisms. These factors are closely intertwined because mitochondria are a major source of pro-oxidant species and are the major intracellular recipients of iron. How iron is transported to mitochondria, however, is largely unknown. Some studies suggest that trafficking through endocytosis may participate to mitochondrial iron delivery with a "kiss and run" mechanism. Intracellular transferrin levels increase in PD, possibly as a consequence of oxidation of iron-containing prosthetic groups in mitochondria. It is therefore conceivable that transferrin endocytic trafficking can contribute to noxious iron accumulation. This short review will summarize these findings and discuss their relevance for a better understanding of PD pathogenesis.