204 - Neuroglobin Overexpression Promotes Mitochondrial Fusion and Prevents Mitochondrial Network Fragmentation in SHSY5Y Cells Subjected to Pro-apoptotic Conditions

Abstract

Oxidative stress and hypoxia play a central role in neuronal injury and cell death in acute and chronic pathological conditions. Neuroglobin (NGB) is a monomeric heme-protein found in neurons that, when overexpressed, confers resistance to apoptosis cause by oxidative stress, hypoxia, and neurotoxicity. Although NGB has been traditionally considered a cytoplasmic protein, recent findings indicate that NGB can localize to mitochondria. However, we have an incomplete understanding of the details of NGB’s mitochondrial interactions and effects. Here, we investigated the effect of NGB overexpression on mitochondrial network morphology in SHSY5Y neuroblastoma cell line using a quantitative approach to measure mitochondrial network features including network size, branch length, and the overall abundance of mitochondria. We found that NGB overexpression caused the formation of larger and more highly branched mitochondrial networks and greater mitochondrial abundance. NGB overexpression also prevented mitochondrial fragmentation, an early event in the apoptotic pathway, in cells exposed to hypoxia, hypoxia/reperfusion, or hydrogen peroxide treatment. These data demonstrate interactions between NGB and mitochondrial fusion/fission processes. We are now exploring whether this effect is due to a direct interaction between mitochondria and Ngb, or involves cytosplasmic signaling pathways. Taken together, these observations have the potential to open new avenues to develop therapeutic strategies against neurodegenerative disease, where dysfunctional mitochondrial dynamics represent a common and prominent early pathological feature.