Abstract：
:Yeast ataxin-2, also known as Pbp1 (polyA binding protein-binding protein 1), is an intrinsically disordered protein implicated in stress granule formation, RNA biology, and neurodegenerative disease. To understand the endogenous function of this protein, we identify Pbp1 as a dedicated regulator of TORC1 signaling and autophagy under conditions that require mitochondrial respiration. Pbp1 binds to TORC1 specifically during respiratory growth, but utilizes an additional methionine-rich, low complexity (LC) region to inhibit TORC1. This LC region causes phase separation, forms reversible fibrils, and enables self-association into assemblies required for TORC1 inhibition. Mutants that weaken phase separation in vitro exhibit reduced capacity to inhibit TORC1 and induce autophagy. Loss of Pbp1 leads to mitochondrial dysfunction and reduced fitness during nutritional stress. Thus, Pbp1 forms a condensate in response to respiratory status to regulate TORC1 signaling.
journal_name
Celljournal_title
Cellauthors
Yang YS,Kato M,Wu X,Litsios A,Sutter BM,Wang Y,Hsu CH,Wood NE,Lemoff A,Mirzaei H,Heinemann M,Tu BPdoi
10.1016/j.cell.2019.02.043subject
Has Abstractpub_date
2019-04-18 00:00:00pages
697-710.e17issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(19)30226-0journal_volume
177pub_type
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