ArticleThe Journal of clinical investigation2025
Uromodulin modulates mitochondria and kidney tubule resilience.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Uromodulin is the most abundant protein in human urine, playing diverse roles, from providing frontline defense against uropathogens to regulating electrolyte balance via modulation of ion channels and cotransporters. In this issue of the JCI, Nanamatsu et al. unveil an alternatively spliced isoform of uromodulin that was dynamically induced in response to oxidative stress and tubular injury. Unlike the canonical secreted form, this isoform was retained in the cell, where it interacted with solute carrier proteins primarily localized to the mitochondrial membrane. Through these interactions, it modulated mitochondrial energetics and enhanced tubular cell resilience to injury. These findings broaden our understanding of uromodulin's multifaceted functions, uncover an adaptive mechanism by which the kidney responds to cellular stress, and open avenues for therapeutic strategies targeting kidney injury and repair.
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