期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12816-z
关键词
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资金
- NIH/NIGMS [R01GM102491]
- Leona M. and Harry B. Helmsley Charitable Trust
- Dr. Frederick Paulsen Chair/Ferring Pharmaceuticals
- George E. Hewitt Foundation for medical research
- Anderson Foundation
- Pioneer Fellowship
- Waitt Advanced Biophotonics Core Facility of the Salk Institute
- NIH-NCI [CCSG: P30 014195]
- NINDS Neuroscience Core Grant [NS072031]
- Waitt Foundation
- Mass Spectrometry Core of the Salk Institute
- NIH
- NCI Cancer Center Support Grant P30 [CA014195]
- NIH F32 fellowship [GM123685]
Cellular homeostasis relies on having dedicated and coordinated responses to a variety of stresses. The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a common stress that triggers a conserved pathway called the unfolded protein response (UPR) that mitigates damage, and dysregulation of UPR underlies several debilitating diseases. Here, we discover that a previously uncharacterized 54-amino acid microprotein PIGBOS regulates UPR. PIGBOS localizes to the mitochondrial outer membrane where it interacts with the ER protein CLCC1 at ER-mitochondria contact sites. Functional studies reveal that the loss of PIGBOS leads to heightened UPR and increased cell death. The characterization of PIGBOS reveals an undiscovered role for a mitochondrial protein, in this case a microprotein, in the regulation of UPR originating in the ER. This study demonstrates microproteins to be an unappreciated class of genes that are critical for inter-organelle communication, homeostasis, and cell survival.
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