EIPOD fellowship under Marie Sklodowska-Curie Actions COFUND
Germany
Citation
Journal: Nat Commun / Year: 2024 Title: Ribosomes hibernate on mitochondria during cellular stress. Authors: Olivier Gemin / Maciej Gluc / Higor Rosa / Michael Purdy / Moritz Niemann / Yelena Peskova / Simone Mattei / Ahmad Jomaa / Abstract: Cell survival under nutrient-deprived conditions relies on cells' ability to adapt their organelles and rewire their metabolic pathways. In yeast, glucose depletion induces a stress response mediated ...Cell survival under nutrient-deprived conditions relies on cells' ability to adapt their organelles and rewire their metabolic pathways. In yeast, glucose depletion induces a stress response mediated by mitochondrial fragmentation and sequestration of cytosolic ribosomes on mitochondria. This cellular adaptation promotes survival under harsh environmental conditions; however, the underlying mechanism of this response remains unknown. Here, we demonstrate that upon glucose depletion protein synthesis is halted. Cryo-electron microscopy structure of the ribosomes show that they are devoid of both tRNA and mRNA, and a subset of the particles depicted a conformational change in rRNA H69 that could prevent tRNA binding. Our in situ structural analyses reveal that the hibernating ribosomes tether to fragmented mitochondria and establish eukaryotic-specific, higher-order storage structures by assembling into oligomeric arrays on the mitochondrial surface. Notably, we show that hibernating ribosomes exclusively bind to the outer mitochondrial membrane via the small ribosomal subunit during cellular stress. We identify the ribosomal protein Cpc2/RACK1 as the molecule mediating ribosomal tethering to mitochondria. This study unveils the molecular mechanism connecting mitochondrial stress with the shutdown of protein synthesis and broadens our understanding of cellular responses to nutrient scarcity and cell quiescence.
Entire : Non-translating S. pombe ribosome large subunit
Entire
Name: Non-translating S. pombe ribosome large subunit
Components
Complex: Non-translating S. pombe ribosome large subunit
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Supramolecule #1: Non-translating S. pombe ribosome large subunit
Supramolecule
Name: Non-translating S. pombe ribosome large subunit / type: complex / ID: 1 / Parent: 0
Source (natural)
Organism: Schizosaccharomyces pombe 972h- (yeast)
Molecular weight
Theoretical: 3.5 MDa
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Concentration
0.25 mg/mL
Buffer
pH: 7.4
Grid
Model: Quantifoil R2/1 / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 0.2 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec.
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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