Human mitoribosome biogenesis and its emerging links to disease

Abstract

Mammalian mitochondrial ribosomes (mitoribosomes) synthesize a small subset of pro-teins, which are essential components of the oxidative phosphorylation machinery. Therefore, their function is of fundamental importance to cellular metabolism. The assembly of mitoribosomes is a complex process that progresses through numerous maturation and protein‐binding events coordi-nated by the actions of several assembly factors. Dysregulation of mitoribosome production is in-creasingly recognized as a contributor to metabolic and neurodegenerative diseases. In recent years, mutations in multiple components of the mitoribosome assembly machinery have been associated with a range of human pathologies, highlighting their importance to cell function and health. Here, we provide a review of our current understanding of mitoribosome biogenesis, highlighting the key factors involved in this process and the growing number of mutations in genes encoding mitoribo-somal RNAs, proteins, and assembly factors that lead to human disease.