Mapping of mitochondrial ferritin in the brainstem of Macaca fascicularis

Highlights

• A novel antibody against human FtMt was characterized.

• No cross-reaction of this antibody with FTH was observed.

• FtMt distribution was mapped in the brainstem.

• FtMt was co-localized with catecholaminergic neurons in the VTA, SNc, and LC.

• FtMt distribution pattern suggested its function in Parkinsonism.

Abstract

Mitochondrial ferritin (FtMt), a recently-studied iron storage protein, which we suspect is an important defense against oxidative stress in neurons and elsewhere. The 242-amino acid FtMt precursor protein is cleaved to mature protein (of molecular weight about 22-kDa) in the mitochondrial matrix. Compared with the ubiquitously expressed traditional ferritin (H-ferritin and L-ferritin), FtMt has been found in fewer locations including the testis, heart and brain. Previous studies have reported that the expression of FtMt in mouse and human brain is predominantly localized to neurons and partly to glial cells, and FtMt exerts protective effects on neurons by maintaining normal function and regulates apoptosis in Alzheimer’s disease and Parkinson’s disease. To find out the function of FtMt in neurodegenerative disease, we had a novel antibody made against human FtMt and characterized it via Western blot analysis, immunoabsorption testing, and double immunofluorescence histochemistry. Then we used this new FtMt antibody to map the distribution of FtMt in the monkey brainstem. We demonstrated widespread distribution of FtMt immunoreactivity throughout the monkey brainstem, with variable staining intensity. FtMt immunoreactivity was observed in the extrapyramidal system, sensory trigeminal nerve nuclei, some motor nuclei including ambiguous nucleus, dorsal motor nucleus of the vagus and hypoglossal nucleus, and some dorsal column nuclei such as the gracile nucleus and cuneate nucleus. In addition, double immunohistochemical stainings confirmed that FtMt immunoreactivity was co-localized with catecholaminergic neurons in the locus coeruleus (63.64%), substantia nigra pars compacta (69.18%), and ventral tegmental area (56.89%). The distribution of FtMt which we found in the brainstem implies possible involvement of FtMt in several physiological mechanisms, especially in the catecholaminergic neurons, and the possibility of significant involvement in neurodegenerative disease.