Our Research

Overview

Our laboratory aims to elucidate the mechanisms of degradation, metabolism, and recycling mediated by autophagy. We focus on the degradation and metabolic processes of a wide range of biomolecules, including proteins, RNA, lipids, sugars, and metabolites.

Current main research themes:

Elucidating the mechanisms of metabolism and intracellular transport of degradation product

Identification of novel degradative enzymes functioning in the vacuole

Investigating the substrate specificity and regulatory mechanisms of vacuolar hydrolases

Elucidating the molecular role of autophagy in cellular homeostasis and metabolic regulation

Research Methods

We use yeast (Saccharomyces cerevisiae) as a model organism. Yeast is ideal for molecular studies due to its ease of genetic manipulation.

Major analytical techniques:

• High-purity isolation of vacuoles and autophagic bodies (inner membrane structures of autophagosomes)

• In vitro assays for degradation activity and substrate specificity

• Integrated approaches combining genetics, molecular biology, cell biology, and metabolic analysis

• Analysis of nucleic acids, lipids, metabolites, and ions (through core facilities or collaborative research)

Major Research Achievements

🔹 RNA Degradation

We reported that RNA is extensively degraded through autophagy. We also identified key enzymes involved in RNA degradation, such as RNases and nucleotidases/phosphatases, and clarified the associated degradation and metabolic pathways.

→   EMBO J. 2015 Jan 13;34(2):154-68.   PubMed                    →  Nat Commun. 2021 Apr 19;12(1):2316.  PubMed

🔹 Metal Ion Recycling

We demonstrated that autophagy is induced under zinc or iron deficiency, and that intracellular recycling of these metal ions is essential for cell survival. Our findings highlight the importance of autophagy in metal ion homeostasis.

 →  J Biol Chem. 2017 May 19;292(20):8533-8543.  PubMed                     →  J Biol Chem. 2017 May 19;292(20):8520-8530.  PubMed

🔹 Purification of Autophagic Bodies

Using our high-purity vacuole isolation technique, we established a method to isolate autophagic bodies accumulated in yeast. This was the first report in the world to purify the inner membrane structures of autophagosomes.

 →  J Biol Chem. 2022 Dec;298(12):102641.   PubMed

🔹 Lipid Degradation

We biochemically demonstrated that Atg15, a vacuolar hydrolase, possesses phospholipase B activity. Furthermore, we showed that proteases localized in the vacuole (Pep4, Prb1) are essential for the activation of Atg15.

→  J Cell Biol. 2023 Dec 4;222(12):e202306120.   PubMed