【Seminar】30 Years of Autophagy: From Fundamental Mechanisms to Healthspan Extension

■Speaker■

Tamotsu Yoshimori, Professor Emeritus of Osaka University,
Professor of The DAICEL Endowed Chair in Beyond Cell Reborn Research, Graduate School of Medicine, Osaka University

■Abstract■

Autophagy is an evolutionarily conserved membrane trafficking pathway that delivers cytoplasmic components to lysosomes for degradation. Major advances in this field followed the identification of autophagy-related (ATG) genes in yeast in 1993 by Yoshinori Ohsumi, which led to rapid expansion of autophagy research and the Nobel Prize in Physiology or Medicine in 2016.

Since joining Ohsumi’s laboratory in 1996, I have spent the past 30 years extending these discoveries from yeast to mammals, focusing on the molecular mechanisms and physiological roles of autophagy. We identified LC3 as an autophagosome-binding protein, enabling the first visualization of autophagosomes in living cells. LC3 has since become the gold-standard marker in the field.

Our work revealed that autophagosomes form at endoplasmic reticulum–mitochondria contact sites and that autophagy selectively eliminates invading pathogens by sensing endosomal membrane damage. We also identified lysophagy, the selective removal of damaged lysosomes, which suppresses nephropathy in hyperuricemic mice.

We further identified Rubicon as a negative regulator of autophagy, showing that its accumulation contributes to metabolic liver disease and age-dependent autophagy decline. Rubicon suppression extended lifespan and ameliorated age-associated phenotypes, including Parkinson’s disease, positioning autophagy as a key target for health-span extension.

Building on these findings, we founded AutoPhagyGO to translate autophagy research into drug discovery and autophagy-activating supplements, including products derived from the traditional Japanese fermented tea Awa-bancha.

■Keywords■

Autophagy, Rubicon, Longevity, Awabancha

Contact

Eriko Okamatsu, Yamamoto Unit RUA