Defective Ribosome Recycling: A Bridge Between Translation Fidelity, Organelle Dysfunction, and Diseases

Abstract

Ribosome recycling is a fundamental biological process crucial for cellular health. Defective recycling disrupts ribosome biogenesis and organelle function, particularly in mitochondria, contributing to ribosomopathies, neurodegenerative diseases, and cancer. While not directly linked to human diseases via known genetic mutations, emerging evidence suggests a critical interplay between ribosome recycling and organelle quality control. Impaired ribosome recycling leads to aberrant ribosome production, compromised translational quality control, protein misfolding, and subsequent organelle dysfunction and cellular stress. These cascading defects underscore the critical need for effective ribosome reutilization, especially under stress, as disruptions can cause translational arrest and heightened stress signaling, perturbing cellular homeostasis. Our analyses establish an indirect but significant link between ribosome recycling and human disease, offering new perspectives on how translational fidelity and organelle maintenance converge to support cellular well-being.