Horie Laboratory (Horie Lab) was established in 2025 at the Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo.
Our research focuses on fundamental studies in life sciences, with a particular emphasis on autophagy. We are dedicated to advancing cutting-edge research on the mechanisms of biomolecular degradation within cells.
In recent years, the Sustainable Development Goals (SDGs) have attracted considerable attention worldwide. Similarly, within living organisms, maintaining a sustainable balance between "synthesis" and "degradation" is crucial. Autophagy plays a central role in this "degradation" process and can be considered an intrinsic SDG system within our bodies.
Autophagy operates continuously in our bodies. When cells experience stress, such as nutrient deprivation, autophagy is strongly induced, leading to the formation of double-membrane structures called autophagosomes. These autophagosomes encapsulate various cellular components, such as proteins and organelles like mitochondria. Subsequently, the autophagosomes fuse with the vacuole in yeast and plants, or with lysosomes in animal cells, where their contents are broken down by various hydrolytic enzymes. This degradation process represents the core function of autophagy.
Autophagy is an evolutionarily conserved process observed in organisms ranging from yeast, flies, and fish to humans and plants. Since the discovery of Atg proteins by Dr. Yoshinori Ohsumi, our understanding of the molecular mechanisms underlying autophagosome formation has significantly progressed.
However, the understanding of the actual "degradation" events has lagged behind. Traditionally, autophagy was considered primarily a protein degradation system. Yet, cells also contain other macromolecules, such as RNA, lipids, sugars, and metabolites. When, where, and how these components are degraded remains incompletely understood.
Our laboratory focuses on autophagy as a degradation system. The degradation occurs within vacuoles or lysosomes. We aim to identify the specific degradative enzymes functioning in these organelles, clarify their regulatory mechanisms and substrate specificities, and uncover the processes and outcomes of degradation.
Currently, our research extends beyond proteins to encompass RNA, lipids, sugars, and metabolites, striving for a comprehensive understanding of the molecular mechanisms behind biomolecular degradation.
We use yeast (Saccharomyces cerevisiae) as a model organism for our studies. Yeast offers excellent advantages: it is easy to genetically manipulate and allows rigorous experimental validation. Notably, many of the fundamental factors involved in autophagy (Autophagy Proteins: Atg proteins) were originally discovered in yeast, establishing the basis of autophagy research. Using yeast enables us to precisely trace the autophagic degradation process by integrating genetic, cell biological, and biochemical approaches.
A particular strength of our laboratory is our technology for isolating vacuoles, the degradation compartments, with high purity from yeast cells. This enables us to directly measure degradative activities and analyze substrates using isolated vacuoles. We are also expanding this research to investigate how degraded biomolecules are subsequently metabolized, recycled, and transported within the cell. By taking on the unexplored field of autophagic degradation processes, we aim to ultimately extend our findings to more complex eukaryotic systems.
Ultimately, our goal is to map the entire landscape ("Atlas") of biomolecules that are degraded, metabolized, and transported via autophagy. We aim to demonstrate that autophagy forms an essential branch of the cellular metabolic network. By exploring the fundamental life phenomenon of biomolecular degradation, we seek to deepen our understanding of the essence of life itself.
