HADHA

Cilia effects upon perturbation of HADHA

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.61) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

cilia associated gene, cytosol, mitochondria

Functional category

• Ciliary assembly/disassembly; Metabolism

Function

Here, we report that HADHA dysfunction markedly impairs primary ciliogenesis and disrupts cilia-dependent signaling. Loss of HADHA reduces both ciliary frequency and length, accompanied by decreased levels of key ciliary signaling mediators. Reintroduction of wild-type HADHA in HADHA knockout cells rescues these defects, whereas its dehydrogenase deficiency mutant (E510Q) fails to restore either normal cilia formation or ciliary signaling. Notably, supplementation with sodium acetate, which resupplies intracellular acetyl-CoA, effectively rescues primary cilium in HADHA-deficient cells. Importantly, this acetate-mediated rescue implicates a potential therapeutic strategy for HADHA-related disorders, supporting the translational relevance of modulating acetyl-CoA levels to restore ciliary function. These findings suggest a relevant link between mitochondrial β-oxidation and primary ciliogenesis, highlighting acetyl-CoA as a potential therapeutic target for disorders related to HADHA deficiency.; Mitochondrial fatty acid $\beta$-oxidation enzyme. Implicated in Ciliopathy via altered cellular energy/metabolism which affects ciliary maintenance(41120337).