Mitochondrial dysfunction, iron accumulation, and ferroptosis in Parkinson’s disease

Abstract

Iron accumulation and ferroptosis have long been implicated in the pathogenesis and neuronal loss of Parkinson’s disease. With the growing discovery of genes associated with Parkinson’s disease and mitochondrial function, there is emerging evidence of the convergent role of mitochondrial dysfunction, subsequent reactive oxygen species generation and ensuing iron accumulation working in concert to facilitate neuronal loss and injury in Parkinson’s disease. This subsequently leads to a vicious cycle where mitochondrial dysfunction may stimulate iron accumulation and inflammation as part of a synergistic feed-forward cycle resulting in neuronal death after the antioxidant cellular defense systems are overwhelmed. We reviewed the existing literature on mitochondrial and iron homeostasis and described the potential intersections of the disease mechanisms leading to iron accumulation, ferroptosis and dopaminergic cell death, ultimately culminating in the onset and progression of Parkinson’s disease.