Loss of centriolar OFD1 activates the p53–DRAM1 pathway to remodel centriolar satellites and suppress ciliogenesis

Autophagy is a lysosome-based proteolytic system that is essential for cellular homeostasis. However, it remains unclear whether autophagy regulates the homeostasis of non-membranous organelles, such as centrosomes. We herein provide evidence to show that the depletion of centrosomes by centrinone, a PLK4 inhibitor, appears to activate autophagy. We then searched for centrosomal proteins whose loss promotes autophagy. Among the centrosomal proteins examined, the loss of OFD1, a centriole and centriolar satellite protein, was the most strongly associated with increases in autophagy markers. Mechanistically, OFD1 was found in close proximity to p53 at the distal ends of centrioles. The loss of OFD1 was associated with the redistribution of p53 from centrioles to the nucleus, leading to the transcriptional induction of the p53 target gene, DNA damage-regulated autophagy modulator 1 (DRAM1). DRAM1 localizes to the pericentrosomal region and is associated with reduced levels of centriolar satellites, including PCM1, CEP131, and CEP290, which are essential for ciliogenesis. Consequently, DRAM1 activation suppressed primary cilium formation. These results support a model in which the OFD1–p53–DRAM1 axis may contribute to linking centrosome integrity with the autophagy-mediated regulation of centriolar satellites and ciliogenesis.