Beyond core cellular function, this is critical for understanding rare human disease. Alternate protein isoforms are selectively mutated in genetic disorders. You can't interpret these mutations without understanding the isoforms and they are central to the unique clinical symptoms.

This alternate decoding isn't just happening in human cells. It is deeply conserved with dual mitochondria and cytoplasmic variants across metazoa, fungi, and plants. However, organisms that have dispensed with aspects of mitochondrial function have lost these mitochondrial variants.

This isn't just for 1 gene. New work from @jimmy-ly.bsky.social identifies hundreds of differentially localized translational isoforms, including >100 that impact the mitochondria.

Tomorrow: We trace the ancient origins of this behavior and its impact on human disease.

Friday: Preprint drops!

Key activities are needed in both the mitochondria and host cell. So how do you put 1 protein in 2 places?

1) Make 2 genes w different signals, or
2) Decode a single RNA to make 2 proteins.

Our new work highlights how alternate translation initiation can create differentially localized proteins.

Countdown to an epic new pre-print.

Mitochondria are cells within our cells. They need the same core activities - replication, transcription, translation. How do cells enable these diverse activities in both compartments? We uncover an unexpected + broad strategy with ancient origins. Stay tuned!