Title: Cytosolic Ribosomal Protein Haploinsufficiency affects Mitochondrial Morphology and Respiration

Abstract:

The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Significant mitochondrial morphological differences, upregulation of glutathione transferases, and SKN-1–dependent oxidative stress resistance were observed across mutants. Loss of a Datasingle rps-10 copy reduced mitochondrial activity, energy levels, and oxygen consumption, mirrored by similar reductions in mitochondrial activity and energy levels in lymphoblast cells with 50% lower RPS10 transcripts. Both systems exhibited altered translation efficiency (TE) of mitochondrial electron transport chain components, suggesting a conserved mechanism to adjust mitochondrial protein synthesis under ribosomal stress. Finally, mitochondrial membrane and cytosolic RPs showed significant RNA and TE covariation in lymphoblastoid cells, highlighting the interplay between protein synthesis machinery and mitochondrial energy production.

Biography:

Elif Sarinay Cenik received her BS in Molecular Biology and Genetics from Bilkent University in Turkey, followed by her PhD in Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School under the tutelage of Dr. Phillip D. Zamore. She then completed postdoctoral training with Nobelist Dr. Andrew Z. Fire in Genetics and Pathology at Stanford University.