Horie Lab

Staff

Exploring the World of Degradation and Metabolism through Autophagy

At the Horie Laboratory, we study the mechanisms of intracellular degradation, with a central focus on autophagy. Autophagy is a crucial pathway that helps maintain cellular homeostasis by removing and recycling unwanted or damaged components. It is strongly activated under nutrient starvation or stress, but it also operates continuously under normal conditions as a key quality control system. When autophagy is impaired, it can lead to various diseases, including neurodegenerative disorders, cancer, metabolic dysfunction, infections, and aging (see figure 1).

Autophagic degradation occurs in the vacuole in yeast or the lysosome in animal cells. We use the budding yeast Saccharomyces cerevisiae as a model organism due to its ease of genetic manipulation and its historical contribution to autophagy research. Yeast provides a powerful system for uncovering the basic principles of this process.

By isolating highly purified vacuoles from yeast, we conduct in vitro assays to measure degradation activity and to identify the enzymes involved as well as the resulting degradation products. This approach enables us to investigate how a broad range of biomolecules—including proteins, RNA, lipids, sugars, ions, and metabolites—are broken down and recycled. In addition to degradation itself, we are particularly interested in the subsequent steps: how the breakdown products are reintegrated into metabolic pathways and how they are transported and reused within the cell (see figure2). Through this work, we aim to construct a comprehensive picture of how cells manage the degradation, metabolism, and transport of biomolecules. By viewing autophagy through the lens of cellular metabolism, we hope to gain deeper insights into its role in maintaining cellular function. In the future, we plan to extend our findings to animal cells and systems.

Selected publications

• Kagohashi Y, Sasaki M, May AI, Kawamata T, Ohsumi Y. The mechanism of Atg15-mediated membrane disruption in autophagy.. J Cell Biol. 2023, Dec 4;222(12):e202306120.
• Kawamata T, Makino S, Kagohashi Y, Sasaki M, Ohsumi Y. A method for the isolation and characterization of autophagic bodies from yeast provides a key tool to investigate cargos of autophagy. J Biol Chem. 2022 Dec;298(12):102641.
• Huang H, Kawamata T, Horie T, Tsugawa H, Nakayama Y, Ohsumi Y, Fukusaki E. Bulk RNA degradation by nitrogen starvation-induced autophagy in yeast. EMBO J. 2015 Jan 13;34(2):154-68.

Horie Lab Website

Access / S2 building, 3F West (Suzukakedai Campus)