Uncovering the role of Fis1 splicing variants in mitochondrial dynamics

Abstract Abstract Mitochondrial fission protein 1 (FIS1) is the principal recruiter of Dynamin-related protein 1 (DRP1) in yeasts but its function in mammalian mitochondrial division remains doubtful. In the process of evolution, mammalian cells developed other DRP1 receptors such as Mff and MiD49/51, which are now thought to be the dominant DRP1 adaptors in higher eukaryotes. Early studies demonstrated that FIS1 deletion prevented mitochondrial fission and overexpression induced fission activity and caused mitochondrial fragmentation in mammalian cells. Later evidence indicates that FIS1 is not needed for fission of mitochondria in mammals but instead may have functions in autophagy and mitochondria-lysosome dynamics. Mammalian genes have intricate control of alternative splicing, which explains potential heterogeneity among tissues and cell types. Early experiments in our lab revealed distinct splicing types of the murine and human Fis1 genes. Importantly, splicing variants of murine Fis1 were found to be regulated by the ubiquitin-proteasome system (UPS) differently and possibly may differently modulate mitochondrial morphology. Key words: Fission Protein 1, Mitochondria, Splicing variants, Fission machinery