Mitochondrial Microproteins: Emerging Regulators in Neurodevelopment and Neurodegeneration

Recent advances in genomics uncovered a large number of microproteins, which are peptides of less than 100 amino-acids encoded by small open reading frames. In contrast to their identification, the validation of the functions of microproteins remains challenging. Especially, what are their biological functions in the cell and how this relates to disease conditions are still largely unknown. Although microproteins ensure a plethora of cellular functions, recent evidence demonstrate that they may disproportionately affect cellular metabolism. In this review, we will address the roles of mitochondrial-targeted microproteins, and especially how this class of protein regulates neuronal metabolism in neurodevelopment and neurodegeneration, and may contribute to axonal and dendritic metabolic disorders.