Danielle Grotjahn, associate professor at Scripps Research, and her team have been recognized by the Journal of Cell Biology for their paper, “Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import,” for garnering exceptional reader interest. This paper is one of 13 featured publications in the journal’s prestigious “The Year in Cell Biology: 2025” collection, which highlights a variety of studies on cellular functions.

Grotjahn’s paper addresses a fundamental question in cell biology: How do proteins made outside of mitochondria get transported inside these essential organelles? While scientists have long known that most mitochondrial proteins are produced by ribosomes in the cell’s cytoplasm, the precise mechanisms governing how some proteins are imported while still being synthesized—a process called co-translational import—have remained mysterious.

Using advanced imaging techniques, Grotjahn and her team captured unprecedented views of ribosomes interacting with mitochondria in their native cellular environment. Ya-Ting (Atty) Chang, in particular, a member of the Grotjahn laboratory and a graduate student at the Skaggs Graduate School of Chemical and Biological Sciences, developed innovative tools to identify ribosomes positioned on mitochondrial membranes in configurations optimal for protein import. This approach enabled the team to produce the first-ever subtomogram average structure—a 3D image processing technique that allows researchers to examine structures more closely by computationally extracting and averaging many copies of the same molecule of interest—of a cytoplasmic ribosome sitting on a mitochondrial surface. Prior imaging techniques captured molecules that had been extracted from their cellular environment—akin to listening to a symphony perform but only hearing the violin. Grotjahn’s advanced techniques allow researchers to listen to the entire symphony and explore its dynamic nature, rather than just one instrument.

The team found that ribosomes attach to the outer mitochondrial membrane at three contact points and cluster together in groups. These clusters gather at spots where the mitochondrial outer and inner membranes pinch closer together, suggesting that mitochondria may reshape themselves locally to help usher proteins inside more efficiently. This work has significant implications for understanding mitochondrial dysfunction, which underlies numerous diseases, including neurodegenerative disorders and cancer. By revealing the molecular architecture of protein import machinery, the research opens new avenues for investigating how disruptions to these processes contribute to disease.