Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 323, Issue 6, Pages C1697-C1703Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00370.2022
Keywords
chemical chaperone; molecular chaperone; proteostasis; renal physiology; unfolded protein response (UPR)
Categories
Funding
- National Institutes of Health (NIH) [R01 DK117126]
- NIH [R35 GM131732]
- O'Brien Pittsburgh Center for Kidney Research [P30DK079307]
- Cystic Fibrosis Foundation [BRODSK21I0, K12 HD052892]
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All cell types respond to stress by inducing protective pathways, with the endoplasmic reticulum (ER) being particularly sensitive to stress. The unfolded protein response (UPR) is a specialized ER stress response pathway that protects against damaged proteins and toxic chemicals. Recent research has linked ER stress and the UPR to acute kidney injury (AKI), a common disease in hospitalized individuals.
All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress-sensitive, primarily because this organelle folds, posttranslationally processes, and sorts one-third of the proteome. In the 1990s, a specialized ER stress response pathway was discovered, the unfolded protein response (UPR), which specifically protects the ER from damaged proteins and toxic chemicals. Not surprisingly, UPR-dependent responses are essential to maintain the function and viability of cells continuously exposed to stress, such as those in the kidney, which have high metabolic demands, produce myriad protein assemblies, continuously filter toxins, and synthesize ammonia. In this mini-review, we highlight recent articles that link ER stress and the UPR with acute kidney injury (AKI), a disease that arises in -10% of all hospitalized individuals and nearly half of all people admitted to intensive care units. We conclude with a discussion of prospects for treating AKI with emerging drugs that improve ER function.
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