FIGURE

Fig. 7

ID

ZDB-FIG-260805-111

Publication

Yi et al., 2026 - HUWE1 targets mitochondria via RMC1 to promote neurodevelopment

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Fig. 7

Working model of the HUWE1–RMC1 pathway and mitophagy-targeted therapy using Urolithin (A) for HUWE1-associated XLID. In normal state, HUWE1 is recruited to mitochondria by the RMC1–AMBRA1 axis. HUWE1 ubiquitylates mitochondrial proteins such as MFN2 and VDAC1/2, keeping mitochondrial proteins in check and allowing brains to develop normally (Top-Left panel). In the disrupted state caused by HUWE1 variants, noncatalytic variants linked to XLID bind RMC1 poorly (Lower-Left panel). As a result, HUWE1 does not localize to mitochondria, mitochondrial proteins accumulate, and brains show developmental defects (Lower-Left panel). Urolithin A treatment restores the degradation of HUWE1 substrates. This intervention partially ameliorates the neurodevelopmental impairments induced by HUWE1 variants (Right panel).

Expression Data

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Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Proc. Natl. Acad. Sci. USA