Jun-ichi Sakamaki

Associate Professor, Graduate School of Medicine, Juntendo University *Profile is at the time of the award.

2024Inamori Research GrantsBiology & Life sciences

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Research topics: Study on the generality, molecular mechanisms, and biological significance of ubiquitination of organellar membrane lipids

Keyword

Summary: Covalent attachment of ubiquitin to proteins is a common post-translational modification involved in various biological processes. It has long been thought that substrates of ubiquitin are restricted to proteins. We have discovered that the ubiquitin protein is covalently conjugated to phospholipids in organellar membranes. However, the molecular mechanism and biological role of phospholipid ubiquitination are unknown. This study aims to understand the underlying molecular basis, biological significance, and its relevance to diseases.

Message

The primary objective of this study is to elucidate the regulatory mechanisms of organellar function, with a particular focus on the unconventional role of ubiquitin as a modifier of membrane lipids.

Outline of Research Achievements

This study aims to elucidate the generality, molecular mechanisms, and biological significance of membrane lipid ubiquitination. I discovered a novel lipid ubiquitination induced by organelle stress. I identified the ubiquitin ligase responsible for this modification and found that it plays an important role in organelle quality control. In addition, I identified candidate target lipids and found that inhibition of the lipid-synthesizing enzyme caused phenotypes similar to those observed in cells lacking the ubiquitin ligase. Collectively, these findings suggest that membrane lipid ubiquitination is a widespread modification system in cells and plays an important role in the regulation of organelle function.

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