Disrupting mitochondrial β-oxidation by depletion of HADHA impairs primary ciliogenesis.

ABSTRACT: Primary cilia are dynamic signaling hubs essential for cell homeostasis, and defects in ciliogenesis underpin various genetic disorders. Alpha-hydroxyacyl-CoA dehydrogenase (HADHA), a subunit of the mitochondrial trifunctional enzyme, is crucial for long-chain fatty acid β-oxidation and acetyl-CoA production. Although it was recently demonstrated that lipid metabolism modulates primary ciliogenesis, the connection between mitochondrial β-oxidation and primary cilia remains largely unexplored. 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 re

SUBMITTER: Kim JB 

PROVIDER: S-EPMC12541092 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature