Deciphering function and the molecular pathways of a novel identified regulator SFXN‐1.2 in mitochondrial dynamics and its effects on worm behavior and neurodegeneration

Abstract

Mislocalizations of mitochondria and alterations in mitochondrial dynamics are the hallmarks in various neurological diseases. Thus, it is critical to understand how the dynamics of mitochondria are regulated on the molecular level. From a candidate screen (95 genes), we have identified a novel gene called sfxn-1.2 (ortholog of human Sideroflexin 1/3), a mitochondrial protein enriched in neurons associated with Alzheimer's disease and Parkinson's disease. Since the function of sfxn-1.2 in mitochondrial transport at the molecular level is unknown, we aim to dissect the function and the molecular pathways of SFXN-1.2 in mitochondrial dynamics and its effects on worm behavior and neurodegeneration. Through cluster analysis and Kymograph assays, we observed that SFXN-1.2 is associated with significant changes in mitochondrial morphology and trafficking in neurons. Our results suggest a possible direct interaction between UNC-104 and mitochondria. The role of UNC-104 (KIF1A) in mitochondrial transport will have a strong impact because since decades it is thought that KIF5 and KIF1Bα are the only transporters of mitochondria. Our findings also suggest the relation between sfxn-1.2 and unc-104 at genetic and protein levels. Neurodegeneration is common in Alzheimer's disease and Parkinson's disease; our data reveal possible motor neuron defects and sensory neuron defects in sfxn-1.2 mutants. Thus, these investigations will aid to develop novel drugs to target neurological diseases based on defects in mitochondrial transport.