News Releases & Research Results Discovery of a new function of peroxisomes as suppliers of cholesterol to cilia: Elucidation of the mechanism of the onset of ciliopathies caused by cholesterol insufficiency

The results of collaborative research conducted by Associate Professor Tatsuo Miyamoto and Professor Shinya Matsuura of the Research Institute for Radiation Biology and Medicine, Hiroshima University, and others.

• The research group discovered that the organelles peroxisomes supply cholesterol to the primary cilia, which are antenna-like immobile structures that develop on the surface of human cells.
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• It had long been unclear as to how a reduced cholesterol level would affect health, but this research revealed that a reduced cholesterol level in primary cilia causes ciliary dysfunction in the cells of patients with peroxisome biogenesis disorders*.
  * A group of conditions caused by the congenital defects of the genes necessary to assemble peroxisomes, named Zellweger syndrome after the discoverer of the disease. This is a very rare genetic disease, complicated by ciliopathy symptoms such as polycystic kidney and retinitis pigmentosa in addition to the symptoms associated with abnormal lipid metabolism such as severe neuropathy and hepatomegaly.
• Many molecules related to cancers and psychiatric/neurological disorders localize in the primary cilia. The results of the research should contribute to the development of novel therapies not only for ciliopathies, which are rare diseases caused by the congenital defects of the primary cilium-associated genes but also for diseases affecting a large number of people.

This research project was conducted with the support of the Advanced Research & Development Programs for Medical Innovation (PRIME) by AMED.

The results of research were published in The EMBO Journal, published by the European Molecular Biology Organization, on May 5.

Miyamoto T., et al. Ciliary cholesterol insufficiency in the hereditary Zellweger syndrome The EMBO Journal
DOI：10.15252/embj.2019103499