Differential Impacts of Ribosomal Protein Haploinsufficiency on Mitochondrial Function.

Details

• Alternative Title:
  The Journal of Cell Biology, 2025, v. 224, no. 3: Differential Impacts of Ribosomal Protein Haploinsufficiency on Mitochondrial Function.
• Journal Article:
  The Journal of Cell Biology
• Personal Author:
  Surya, Agustian ; Bolton, Blythe Marie ; Rothe, Reed ; Mejia-Trujillo, Raquel ; Leonita, Amanda ; Zhao, Qiuxia ; Arya, Alia ; Liu, Yue ; Rangan, Rekha ; Gorusu, Yasash ; Nguyen, Pamela ; Cenik, Can ; Cenik, Elif Sarinay
• Description:
  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.
• Content Notes:
  Author manuscript
• Subjects:
  • Ribosomal Proteins
  • Haploinsufficiency
  • Mitochondria
  • Caenorhabditis elegans
  • Animals
  • Humans
  • Protein Biosynthesis
  • Caenorhabditis elegans Proteins
  • Oxidative Stress
  • Energy Metabolism
  More +
• Source:
  The Journal of Cell Biology, 2025, v. 224, no. 3
• DOI:
  https://doi.org/10.1083/jcb.202404084
• ISSN:
  0021-9525 ; 1540-8140
• Pubmed ID:
  39786340
• Pubmed Central ID:
  PMC11716151
• Document Type:
  Text
• Funding:
  P40 OD010440/OD/NIH HHSUnited States/ ; F-2133-20230405/Welch Foundation/ ; R35 GM138340/GM/NIGMS NIH HHSUnited States/ ; P40 OD010440/CD/ODCDC CDC HHSUnited States/ ; R35 GM150667/GM/NIGMS NIH HHSUnited States/ ; R35GM138340/GM/NIGMS NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  e202404084(48 pdf pages)
• Volume:
  224
• Issue:
  3
• Download URL:
  https://stacks.cdc.gov/view/cdc/261790/cdc_261790_DS1.pdf
• File Type:
  [PDF - 2.19 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:b7fcb8d2089e78ee67e37d025581e76bfaa1700fded60d7d21f323be3ac20d7a4f313e2a44a856187f076824042b32b777b4c7ffbbbb93669507eb5982f99f88