Researchers developed LOCL-TL, a novel optogenetic tool that uses blue light to control a site-specific biotin ligase, allowing for the precise monitoring of protein translation within specific cellular regions. By applying this method to human mitochondria, the study discovered that approximately 20% of nuclear-encoded mitochondrial genes are synthesized directly at the outer mitochondrial membrane. The findings reveal a dual-strategy system where long proteins are recruited during translation via a bipartite signal, while short proteins are targeted through an AKAP1-mediated process involving mRNA and introns. This translation-independent recruitment of short sequences, which are vital for respiratory chain function, appears to be a unique evolutionary development in mammals not found in yeast. Ultimately, the study demonstrates that localized translation is essential for maintaining mitochondrial protein levels and efficient metabolic activity.

References:

• Luo J, Khandwala S, Hu J, et al. Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation[J]. Cell, 2025, 188(20): 5589-5604. e17.