Mitochondria-targeting siRNA screening identifies mitochondrial calcium uniporter as a factor involved in nucleoid morphology.

This article focuses on the role of the mitochondrial calcium uniporter (MCU) in regulating mitochondrial DNA (mtDNA) nucleoid morphology and mitochondrial function in human cells. Using a custom siRNA library targeting 1,164 mitochondria-related genes in HeLa cells, the study identified MCU as a key factor whose suppression leads to enlarged mitochondrial nucleoids and decreased respiratory activity without altering mtDNA copy number. The findings demonstrate that mitochondrial Ca²⁺ uptake via MCU influences nucleoid morphology, as treatment with a Ca²⁺ ionophore reversed nucleoid enlargement in MCU-deficient cells. This research highlights a novel link between mitochondrial calcium dynamics, mtDNA organization, and respiratory function, and introduces a versatile siRNA library for further exploration of mitochondrial protein functions.