Ribophagy: Selective Ribosome ‘Eating’

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Nature Reviews Molecular Cell Biology | AOP, published online 16 April 2008; doi:10.1038/nrm2401

DOI: 10.1038/nrm2401 prot ein d egra dat ion Ribophagy: selective ribosome ‘eating’

Protein degradation by autophagy degraded by autophagy following autophagy pathways. This implies in yeast involves the sequestering of starvation, Kraft et al. tagged proteins that ribophagy is a specific process …ribosome organelles and other macromolecular of the large and small ribosomal sub- that is not caused by a deficiency in degradation complexes within membrane vesicles, units with green fluorescent protein basal autophagy, and that proteins which are subsequently delivered (GFP) and observed the accumula- of the large and small ribosomal relies on both to the vacuole where the cargo is tion of GFP in the vacuole. This subunit may require different selective and degraded. Autophagy can occur relocalization required components selective degradation machineries. non-selective through a basal, non-selective ‘bulk’ of the basal, non-selective autophagy Also, even though ubp3∆ and bre5∆ autophagy process or can involve an organelle- machinery but was independent of mutant cells died following prolonged specific pathway. However, little is the selective cytoplasm-to-vacuole nutrient starvation and were sensi- processes. known about what determines the autophagic pathway. The ribosomal tive to rapamycin (which inhibits selectivity of autophagy pathways and proteins have increased turnover the nutrient-sensing regulator Tor), how they are regulated. kinetics compared with other cyto- the physiological relevance of the Under nutrient-rich conditions, plasmic proteins, suggesting that ribophagy pathway warrants further large amounts of ribosomal subunits ribosome degradation involves a new investigation. are assembled, which raises the pos- selective autophagy pathway, which A catalytically inactive Ubp3 sibility for the need to remove excess the authors termed ‘ribophagy’. Given mutant was unable to rescue the ribosomes in response to changing that both ribosomal and cytoplasmic ribophagy defect, which suggests environmental circumstances. To protein accumulation in the vacuole that the de-ubiquitylation activity of examine whether ribosomes are was abolished in cells that lacked Ubp3 is essential. Moreover, ubp3∆ the basal autophagy machinery, the mutant cells were enriched in ubiqui- authors concluded that ribosome tylated ribosomal proteins, implying degradation relies on both selec- a deubiquitylation event in the tive and non-selective autophagy regulation of ribophagy. However, it processes. remains unclear which E3 ligases and Next, Kraft et al. screened a collec- ubiquitylated substrates are involved tion of starvation-sensitive mutants in regulating this mechanism of for defects in vacuolar accumulation selective ribosome degradation. of GFP-tagged ribosomal proteins Arianne Heinrichs and identified the ubiquitin protease ORIGINAL RESEARCH PAPER Kraft, C. et al. Ubp3 and its co-factor Bre5. ubp3∆ Mature ribosomes are selectively degraded upon and bre5∆ mutant cells accumulate starvation by an autophagy pathway requiring proteins of the 60S large ribosomal the Ubp3/Bre5p ubiquitin protease. Nature Cell Biol. 6 April 2008 (doi:10.1038/ncb1723) subunit (but not of the 40S small ribo- Further Reading Klionsky, D. J. Autophagy: somal subunit) following starvation, from phenomenology to molecular understanding in less than a decade. Nature Rev. while retaining functional nutrient Mol. Cell Biol. 8, 931–937 (2007) sensing and general trafficking and