Yoshinori Ohsumi

Yoshinori Ohsumi
Ohsumi in 2016
Yoshinori Ohsumi
Born	大隅 良典 9 2, 1945
Birthplace	Fukuoka, Japan
Nationality	Japanese
Occupation	Cell biologist
Employer	Institute of Science Tokyo
Known for	Mechanisms of autophagy
Education	University of Tokyo (BSc, DSc)
Awards	Kyoto Prize (2012) Gairdner Foundation International Award (2015) Nobel Prize in Physiology or Medicine (2016)
Website	[Official laboratory page Official site]

Yoshinori Ohsumi (大隅 良典, Ōsumi Yoshinori; born February 9, 1945) is a Japanese cell biologist whose groundbreaking research into autophagy — the process by which cells break down and recycle their own components — transformed the understanding of fundamental cellular biology. Born in Fukuoka, Japan, Ohsumi spent decades investigating the molecular machinery underlying autophagy, initially using baker's yeast (Saccharomyces cerevisiae) as a model organism to identify genes essential to the process. His work, which began in earnest in the late 1980s and early 1990s, opened an entirely new field of biological research and illuminated mechanisms relevant to a wide range of human diseases, including cancer, neurodegenerative disorders, and infections. In recognition of his discoveries, Ohsumi was awarded the 2016 Nobel Prize in Physiology or Medicine as the sole laureate, one of the most prestigious accolades in science. He also received the Kyoto Prize for Basic Sciences in 2012, the Gairdner Foundation International Award in 2015, and the Breakthrough Prize in Life Sciences in 2017. Ohsumi is a professor at the Institute of Innovative Research at the Institute of Science Tokyo (formerly the Tokyo Institute of Technology).

Early Life

Yoshinori Ohsumi was born on February 9, 1945, in Fukuoka, a city on the northern shore of the island of Kyushu in southern Japan. He grew up in the aftermath of World War II, a period during which Japan was undergoing reconstruction and significant social and economic change. Ohsumi has recounted that as a child he developed an interest in the natural world, spending time observing insects and collecting specimens, activities that fostered an early curiosity about biological systems.

Ohsumi's interest in science deepened as he progressed through his school years. He was drawn to chemistry and biology, disciplines that would later converge in his career as a molecular cell biologist. Despite the modest circumstances of postwar Japan, educational opportunities were expanding, and Ohsumi was able to pursue his academic interests through higher education at some of the country's foremost institutions.

The formative experiences of Ohsumi's youth — his curiosity about natural processes and his early exposure to scientific thinking — laid the groundwork for a career that would ultimately redefine understanding of one of the most fundamental processes in cell biology. While many of his contemporaries gravitated toward the more fashionable fields of molecular biology that were rapidly developing during the 1960s, Ohsumi later chose to investigate comparatively neglected areas of cell biology, a decision that would prove consequential for the field of autophagy research.

Education

Ohsumi pursued his undergraduate education at the University of Tokyo, one of Japan's most prestigious academic institutions, where he earned a Bachelor of Science degree. He continued his graduate studies at the same university, ultimately obtaining a Doctor of Science (DSc) degree.

During his time at the University of Tokyo, Ohsumi was trained in the fields of molecular biology and biochemistry. His doctoral research provided him with the technical skills and theoretical knowledge that would later be instrumental in his autophagy studies. The rigorous academic environment of the University of Tokyo exposed him to a broad range of biological problems and methodological approaches, including work with yeast and other model organisms that would become central to his later career.

Following the completion of his doctoral studies, Ohsumi undertook postdoctoral research at Rockefeller University in New York City, where he gained further experience in cell biology and expanded his international scientific network. This period abroad was formative, exposing him to different research cultures and broadening his scientific perspective before he returned to Japan to establish his own research program.

Career

Early Research and Move to Yeast Biology

After completing his postdoctoral work at Rockefeller University, Ohsumi returned to Japan and joined the faculty of the University of Tokyo, where he began his independent research career. During this period, he worked in the area of cell biology and became increasingly interested in the lysosome and the vacuole, the cellular compartments responsible for degradation and recycling of intracellular materials. In yeast cells, the vacuole serves a function analogous to the lysosome in animal cells, breaking down proteins and other macromolecules for reuse by the cell.

Ohsumi chose to focus on the yeast vacuole at a time when few other researchers were studying it. The vacuole was considered a relatively unimportant organelle — essentially a cellular waste bin — and attracted little attention from the mainstream molecular biology community. Ohsumi, however, recognized that understanding how cells degrade and recycle their own components could yield fundamental insights into cell biology. This willingness to pursue an unfashionable research topic would become one of the defining characteristics of his career.

Discovery of Autophagy Mechanisms in Yeast

The term "autophagy," derived from the Greek words meaning "self-eating," was coined by the Belgian biochemist Christian de Duve in the 1960s to describe the process by which cells enclose portions of their own cytoplasm within membrane-bound vesicles and deliver them to lysosomes for degradation. Although the phenomenon had been observed by electron microscopy, the molecular mechanisms underlying autophagy remained almost entirely unknown for decades. It was Ohsumi's work, beginning in the late 1980s, that transformed autophagy from an obscure morphological observation into a molecularly defined and genetically tractable process.

In a series of experiments conducted in the early 1990s, Ohsumi used Saccharomyces cerevisiae (baker's yeast) to study autophagy. He reasoned that if autophagy occurred in yeast, it should be observable in the vacuole, where degraded material would accumulate. By using yeast strains deficient in vacuolar proteases — enzymes that break down proteins inside the vacuole — Ohsumi was able to trap the autophagic bodies that accumulated when autophagy was induced by nutrient starvation. Using light microscopy, he observed the accumulation of these autophagic bodies inside the vacuole, providing the first clear morphological evidence of autophagy in yeast.

This observation was a critical breakthrough. Having established a system in which autophagy could be visually monitored in yeast, Ohsumi then used random mutagenesis to identify genes required for autophagy. He exposed yeast cells to chemical mutagens and screened for strains in which autophagic bodies failed to accumulate in the vacuole upon starvation, indicating that the autophagy process was disrupted. Through this approach, Ohsumi identified the first ATG (autophagy-related) genes, which encode proteins essential for the initiation, execution, and regulation of autophagy.

By 1993, Ohsumi and his colleagues had identified 15 genes essential for autophagy in yeast. Subsequent work by Ohsumi's laboratory and by other groups, inspired by his discoveries, expanded the number of known ATG genes and began to characterize the protein complexes they encode. These studies revealed a sophisticated molecular machinery that orchestrates the formation of the autophagosome — a double-membraned vesicle that engulfs cytoplasmic material — and its subsequent fusion with the vacuole (or lysosome in animal cells) for degradation.

Elucidation of Autophagy Pathways

Following the identification of the core ATG genes, Ohsumi and his research group undertook a detailed characterization of the protein products of these genes and the biochemical pathways in which they participate. Their work revealed that autophagy is regulated by a cascade of protein complexes, each performing a distinct function in the autophagic process.

Key findings from Ohsumi's laboratory include the discovery that the Atg1 protein kinase complex is required for the initiation of autophagy, that a lipid kinase complex containing Atg6 is involved in the nucleation of the autophagosomal membrane, and that two ubiquitin-like conjugation systems — one involving Atg12 and another involving Atg8 — are essential for the expansion and closure of the autophagosome.

The discovery that autophagy uses ubiquitin-like conjugation systems was particularly notable because it connected autophagy to well-established biochemical mechanisms already known to be important in other cellular processes. This finding provided a conceptual framework for understanding how the autophagosomal membrane is assembled and also offered molecular targets for future experimental and therapeutic intervention.

Importantly, Ohsumi's work demonstrated that the core autophagy machinery is highly conserved from yeast to humans. The ATG genes identified in yeast have functional counterparts (homologs) in mammals, including humans. This evolutionary conservation underscored the fundamental importance of autophagy and meant that the discoveries made in the simple yeast system were directly applicable to understanding human cell biology and disease.

Implications for Human Disease

The identification of the molecular machinery of autophagy by Ohsumi and others opened new avenues of research into the role of autophagy in human health and disease. Disruptions in autophagy have been linked to a broad spectrum of medical conditions, including cancer, Parkinson's disease, Alzheimer's disease, type 2 diabetes, and various infectious diseases.

In cancer, autophagy plays a complex and context-dependent role: it can act as a tumor suppressor by removing damaged organelles and preventing the accumulation of toxic cellular waste, but it can also promote the survival of established tumors by providing nutrients under conditions of metabolic stress. In neurodegenerative diseases, defects in autophagy lead to the accumulation of misfolded proteins that form toxic aggregates, a hallmark of conditions such as Parkinson's and Alzheimer's diseases. Autophagy also plays a role in the immune response, helping cells to eliminate intracellular bacteria and viruses.

The Nobel Assembly at the Karolinska Institutet, in awarding Ohsumi the 2016 Nobel Prize, noted that "mutations in autophagy genes can cause disease" and that "the autophagic process is involved in several conditions including cancer and neurological disease." The Assembly emphasized that Ohsumi's discoveries had "led to a new paradigm in our understanding of how the cell recycles its content."

Autophagy and Fasting: Public Discourse and Misinformation

Ohsumi's Nobel Prize-winning research on autophagy has attracted significant public attention, particularly in the context of fasting and dietary practices. Because autophagy is induced by nutrient deprivation, some commentators and media outlets have drawn connections between Ohsumi's work and the health benefits attributed to fasting, including the claim that fasting triggers autophagy, which in turn may help the body remove damaged cells and reduce inflammation.

However, Ohsumi's research has also been the subject of misinformation. False social media posts with tens of thousands of shares have claimed that Ohsumi recommended fasting as a cure for cancer, a claim that fact-checking organizations have debunked. Ohsumi's research demonstrated that autophagy is a fundamental cellular process activated by starvation conditions, but he did not make clinical recommendations regarding fasting as a treatment for cancer or other diseases.

Academic Positions

Throughout his career, Ohsumi held positions at several Japanese academic institutions. After his initial appointment at the University of Tokyo, he moved to the National Institute for Basic Biology in Okazaki, where he continued his autophagy research. He subsequently joined the faculty of the Tokyo Institute of Technology (now the Institute of Science Tokyo), where he became a professor in the Frontier Research Center (later the Institute of Innovative Research).

At the Institute of Science Tokyo, Ohsumi maintains a laboratory that continues to investigate the molecular mechanisms of autophagy. The Ohsumi Laboratory focuses on understanding the detailed biochemistry and cell biology of the autophagy machinery, including the biogenesis of the autophagosomal membrane and the regulation of autophagy in response to various cellular signals.

In recognition of Ohsumi's contributions to the promotion of fundamental research, the Institute of Science Tokyo established the Yoshinori Ohsumi Award for Fundamental Research, which provides financial support to researchers conducting basic scientific inquiry. The award has been given annually to researchers at the institute, recognizing work that exemplifies the spirit of curiosity-driven research that characterized Ohsumi's own career.

Personal Life

Yoshinori Ohsumi is known among colleagues as a soft-spoken and understated scientist who has consistently advocated for the value of basic, curiosity-driven research over applied or goal-oriented science. In public statements following his Nobel Prize, Ohsumi expressed concern about the increasing emphasis on practical applications in scientific funding, arguing that fundamental discoveries such as those in autophagy research arise from the pursuit of basic questions about how living systems work.

Ohsumi has co-authored scientific publications with Mariko Ohsumi, indicating a collaborative professional relationship.

He resides in Japan and continues to be affiliated with the Institute of Science Tokyo, where he maintains an active research program.

Recognition

Yoshinori Ohsumi has received numerous awards and honors for his contributions to cell biology and the elucidation of autophagy mechanisms. The most significant of these include:

• Kyoto Prize for Basic Sciences (2012): Awarded by the Inamori Foundation for his research into the molecular mechanisms of autophagy, the Kyoto Prize is one of Japan's most prestigious awards for scientific achievement.

• Gairdner Foundation International Award (2015): This Canadian medical science prize recognized Ohsumi's identification of the genes and molecular mechanisms governing autophagy.

• Nobel Prize in Physiology or Medicine (2016): Ohsumi was the sole recipient of the 2016 Nobel Prize in Physiology or Medicine "for his discoveries of mechanisms for autophagy." The Nobel Assembly at the Karolinska Institutet cited his identification of autophagy genes in yeast and his elucidation of the molecular machinery underlying the autophagic process as contributions that "led to a new paradigm in our understanding of how the cell recycles its content."

• Breakthrough Prize in Life Sciences (2017): Awarded for his elucidation of the molecular mechanisms and biological functions of autophagy.

In addition to these major awards, Ohsumi has received recognition from various scientific societies and institutions in Japan and internationally. His Nobel Lecture, delivered at the Karolinska Institutet in Stockholm, provided a comprehensive account of the history of autophagy research and his own contributions to the field.

Legacy

Yoshinori Ohsumi's research fundamentally changed the field of cell biology by establishing autophagy as a genetically and molecularly defined process. Before his work in the early 1990s, autophagy was a poorly understood phenomenon that attracted little scientific attention. The identification of the ATG genes and the subsequent characterization of the autophagy machinery created an entirely new field of research that has grown exponentially. Thousands of researchers worldwide now study autophagy and its implications for human disease, a direct consequence of the tools, concepts, and experimental systems that Ohsumi developed.

The significance of Ohsumi's contributions lies not only in the specific molecular discoveries he made but also in the approach he took to scientific research. By choosing to investigate a neglected area of cell biology using a simple model organism, Ohsumi demonstrated the value of curiosity-driven basic research. His career serves as an example of how fundamental discoveries can emerge from the study of seemingly simple systems when researchers are free to pursue questions driven by intellectual curiosity rather than immediate practical application.

The establishment of the Yoshinori Ohsumi Award for Fundamental Research at the Institute of Science Tokyo reflects this philosophy, providing support for researchers engaged in basic scientific inquiry and promoting the kind of open-ended investigation that characterized Ohsumi's own work.

Ohsumi's discoveries have had direct implications for biomedical research. The understanding that autophagy is involved in processes such as tumor suppression, clearance of intracellular pathogens, and prevention of neurodegenerative disease has opened therapeutic avenues that are being actively explored. Pharmaceutical research targeting components of the autophagy pathway is ongoing, and the clinical significance of autophagy modulation remains an area of intensive investigation.

As the Nobel Assembly stated in its 2016 citation, Ohsumi's work "led to a new paradigm in our understanding of how the cell recycles its content," establishing autophagy as one of the core processes of cell biology alongside other fundamental mechanisms such as protein synthesis, cell division, and apoptosis.