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I'm Noboru Mizushima, and this is why I research.
Noboru Mizushima received his doctoral degree from Tokyo Medical and Dental University where he studied molecular immunology. Following his doctorate, Dr. Mizushima completed post-doctoral studies at the National Institute for Basic Biology (Japan) in the laboratory of Dr. Yoshinori Ohsumi where he studied mammalian and yeast autophagy. As a laboratory head at Tokyo Metropolitan Institute of Medical Science, Dr. Mizushima began extensive investigation of the physiological role of autophagy using mouse genetics, as well as molecular mechanisms of autophagy in mammals. Currently, Dr. Mizushima is a Professor of Biochemistry and Molecular Biology at the University of Tokyo where his laboratory studies autophagy, the lysosome, and intracellular protein/organelle degradation. He is the 2016 recipient of The Uehara Prize, the current President of the Japanese Biochemistry Society, and a Thompson Reuters Citation Laureate, awarded to researchers whose work is worthy of Nobel recognition.
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Would you tell us what sparked your interest in basic science?
Throughout junior high school and high school, physics was one of my favorite subjects as it was sophisticated and logical. Back then, biology was a more descriptive subject as many principles and pathways had yet to be discovered and recognized. It was actually one of my worst subjects! Despite its flaws, I still chose to enter medical school due to my interest in the workings of biological systems in the human body. My interest in biological basic science was sparked then in university when I became exposed to molecular biology (for example, learning something as simple as genes encoding proteins). It provided explanations and gave meaning to the biological phenomena that was taught to me before university; I have only deep respect for basic science ever since.
You have made many important discoveries in Autophagy. Is there on particular experiment or discovery you feel most proud of? An ‘aha moment’?
For me, it would be the discovery of “fertilization-induced autophagy” in mice. That was my own discovery of a critical phenomenon that I had made using a mouse model of my creation. After starting my own lab, we were then able to show that autophagy is essential for preimplantation development (likely functioning as a nutrient supplier). This function had been overlooked when conventional knockout mice were used but became evident in oocyte-specific knockout mice. The process of raising and subsequently solving this research question was highly enjoyable.
Your research has helped characterize the mechanisms regulating autophagy and has driven the field forward. To you, what important questions in the field of autophagy are left unanswered?
Outstanding questions include the site of autophagosome formation, the source of autophagosomal membrane, the composition of the autophagosomal membrane, and the function of autophagy in classical metabolism. Additionally, there is currently still no satisfactory method to measure autophagic activity in vivo.
Tell us more about the questions you and your lab are currently trying to answer and where you see your research moving in the future?
With respect to answering research questions, my lab is now focused on understanding the fusion step between the autophagosome and lysosome as well as the general role of autophagy in vertebrates. We are also working to establish new methods to monitor autophagic flux, for example, a probe to measure autophagic activity in live animals.
Describe why your research is important to the ordinary citizen.
Being part of basic biology, dysregulated autophagy underlies a wide variety of human diseases including cancer and neurological disorders. Elucidating the mechanisms of autophagy will enable us to pinpoint the cause of the disease and/or provide a cure to the disease. This applies to most, if not all, existing biological research. I believe the adage “information is power” to be true. Besides aforementioned translational aspects, we should also remain curious and simply take delight in learning new things in basic biology. This is what I want to share with the ordinary citizen.
Outside of autophagy, what research do you find especially exciting right now?
Quantum mechanics and quantum biology. Advancements in quantum biology will undoubtedly benefit our current understanding of biology since all molecules in organisms should follow the laws of quantum mechanism (in a tiny space, at least). I appreciate how biology can be further simplified. Astrobiology is also fascinating. The prospect that extraterrestrial biological material, if found, could bring some unimaginable exception to known biological concepts is fascinating. I want to know whether the principle of biology that we use on the earth is unique or not.
Tell us why you research? What motivates you to keep forging ahead?
Because it is super-interesting to discover new concepts and principles through doing research.
And finally, if you could have one superpower, what superpower would that be?
None! However, if this question was presented to me a few years ago, I would have answered with “immense memory storage capacity in my brain”. I often have ideas that come and go quickly. Some of them are particularly interesting or hold potential but no matter how hard I try to recall them, I find that I cannot. However, I have realized that the ability to forget is essential for a peaceful life. I am now completely satisfied with my current memory storage capacity! (I will soon forget what I have answered in this interview…)
Select Publications by Dr. Mizushima:
- Tsukamoto S, et al., "Autophagy is essential for preimplantation development of mouse embryos." Science. 321:117-20, 2008.
- Itakura E, et al., "The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes." Cell. 151:1256-69, 2012.
- Jiang P, et al., "LC3- and p62-based biochemical methods for analysis of autophagy progression in mammalian cells.” Methods. 75: 13-18, 15 March 2015.
- Hara T, et al., “Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.” Nature. 441: 885-889, 15 June 2006.
- Kuma A, et al., “The role of autophagy during the early neonatal starvation period.” Nature. 432: 1032-1036, 23 December 2004.
- Mizushima N, et al., “In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker.” Mol Biol Cell. 15(3): 1101-1111, 1 March 2004.
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