Ribosomes hibernate on mitochondria during cellular stress

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Cellular adaptation to nutrient deprivation is crucial for survival.
• Yeast exhibits mitochondrial fragmentation and ribosome sequestration upon glucose depletion.
• The precise mechanism linking mitochondrial stress to protein synthesis shutdown is unclear.

Purpose of the Study:

• To elucidate the molecular mechanism of protein synthesis shutdown during nutrient stress in yeast.
• To investigate the structural basis of ribosome-mitochondria interactions under starvation conditions.
• To identify the factors mediating the tethering of hibernating ribosomes to mitochondria.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) for ribosome structure determination.
• In situ structural analyses to visualize ribosome-mitochondria complexes.
• Biochemical assays to identify protein interactions.

Main Results:

• Glucose depletion halts protein synthesis, with ribosomes lacking tRNA and mRNA.
• Hibernating ribosomes form higher-order oligomeric arrays on the outer mitochondrial membrane.
• Ribosomal protein Cpc2/RACK1 mediates the tethering of ribosomes to mitochondria via the small ribosomal subunit.

Conclusions:

• The study reveals a novel mechanism connecting mitochondrial stress to protein synthesis inhibition.
• Hibernating ribosomes are stored on mitochondria through specific protein interactions, facilitating cell quiescence.
• This provides insights into cellular responses to nutrient scarcity and the regulation of protein synthesis.