Interesting work!! One caveat while the abstract mentions that mitochondrial proteins show kinetic properties that "do not reflect co-translational targeting". If you look at the subset of mito localized RNAs (Fazal et al 2019), they seem to have kinetic properties indicative of membrane targeting.

🎯 The proof: When we removed TIM50's proline stretch, many of these problems improved, including reduced protein synthesis for many mitochondrial proteins. This suggests the ribosome traffic jam is the main culprit, not direct effects of eIF5A on other mito proteins. (6/7)

🚨 The fallout: This triggers the mitoCPR stress response and mitochondrial proteins pile up in "MitoStores" - cytosolic storage deposits containing cellular chaperones like Hsp104. Many mito proteins get translationally downregulated, even ones without proline stretches! (5/7)

📍 Location matters: TIM50's mRNA sits right at the mitochondrial surface ( doi.org/10.7554/eLif...). When ribosomes stall during cotranslational import, it creates a bottleneck exactly where new proteins need to enter mitochondria. (4/7)

🎯 Our focus: TIM50, a mitochondrial import receptor with 7 consecutive prolines. When eIF5A is depleted, ribosomes get seriously stuck here - creating a traffic jam up to 300 base pairs long!