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1 Okayama University Medical Research Updates (OU MRU) Vol.66 Source: Okayama University (JAPAN), Public Relations and Information Strategy For immediate release: 25 March 2019 Okayama University research: Is too much protein a bad thing? (Okayama, 25 March) In a recent study published in elife scientists at Okayama show how proteins can hamper an organism s growth. Biochemists have shown that very high protein levels can be harmful to cells in the human body. However, exactly which proteins fall under this category remains a mystery. Mr.Yuichi Eguchi(graduate student) and Associate Professor Hisao Moriya s research team at Okayama University recently reported a framework for discriminating between which proteins are toxic at excessive levels and which are not. The theory behind this phenomenon, also known as the protein burden, is that accumulation of excessive protein within the cell will deplete the cell of resources, such as energy. The limit required to reach this burden though, is not the same for all proteins. Green fluorescent protein (GFP) is a harmless protein artificially introduced into cells for visualizing the insides of the cell. When GFP levels were increased within yeast cells, they found that GFP up to 15% of total protein content was harmless to the cells. Using this measure as a standard, Associate Professor Hisao Moriya s team set out to estimate the burden limit of functional proteins in the cells. 29 proteins essential for energy production were subsequently over produced. While many of these proteins also had limits close to 15%, suggestive of their harmless nature, some of the proteins showed growth retardation and other unpleasant effects at lower levels. One such protein was found to accumulate within the mitochondria. Clogging the mitochondria prevents cells from producing oxygen. Another protein was found to undergo structural changes and aggregate into big pieces. Another reason for some of these proteins having a low burden limit, was due to metabolic disturbances induced when they were produced even slightly higher than usual. When these proteins were inactivated by mutations, their burden limit increased. Lastly, the researchers also found that certain proteins showed growth retardation, even at very low levels. Further investigation revealed that such proteins are programmed to remain at inherently low levels. Therefore, even small changes to their concentrations can be dangerous. This study paved a framework for biologists to make distinctions between proteins based on how toxic they are when present in abnormal amounts. These differences could be attributed to the function, structure or genetic programming for that protein. Scientists can hope to use this framework to investigate proteins that are associated with diseases such as Alzheimer s disease or Parkinson s disease Tsushima-naka, Kita-ku, Okayama Japan
2 Background The protein burden: Each protein has a distinct function within cells. Proteins are found in millions within the cell, and are synthesized or increased when required. Their levels subside when the cell doesn t require them anymore. In certain conditions, such as neurodegenerative disorders, the levels of some proteins inherently remain high. Because the cell is not used to this, a battle to reduce these proteins ensues. This not only uses up the cell s energy but damages the cell in the process. Caption By measuring the expression level that causes growth defect (expression limit), Eguchi and Moriya established a framework to distinguish harmful proteins from harmless proteins upon overexpression. They also found that some proteins were harmful upon overexpression because; they form aggregation through cysteine residues (S S bond), they are transported into mitochondria, and they trigger metabolic perturbation. Reference Yuichi Eguchi Koji Makanae Tomohisa Hasunuma Yuko Ishibashi Keiji Kito Hisao Moriya. Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins. elife, 2018;7:e Reference (Okayama Univ. e Bulletin & OU MRU): Associate Professor Moriya s team e Bulletin Vol.3 (2013):Measuring the copy number limits of all genes in budding yeast. First time ever for any organisms. OU MRU Vol.36 (2017):Overloading of protein localization triggers cellular defects. OU MRU Vol.37 (2017):Protein dosage compensation mechanism unravelled Tsushima-naka, Kita-ku, Okayama Japan
3 Correspondence to Associate Professor Hisao Moriya, Ph.D. Research Core for Interdisciplinary Sciences, Okayama University, Tsushimanaka, Kita ku, Okayama , Japan e mail : hisaom@cc.okayama u.ac.jp u.ac.jp/~hisaom/hmwiki/index.php?topenglish Associate Professor Hisao Moriya Further information Okayama University Tsushima naka, Kita ku, Okayama , Japan Public Relations and Information Strategy E mail: www adm@adm.okayama u.ac.jp Website: u.ac.jp/index_e.html Okayama Univ. e Bulletin: u.ac.jp/user/kouhou/ebulletin/ About Okayama University (YouTube): Okayama University Image Movie (YouTube): Okayama University Medical Research Updates (OU MRU) The whole volume : OU MRU (1 ) Vol.1:Innovative non invasive liquid biopsy method to capture circulating tumor cells from blood samples for genetic testing Vol.2:Ensuring a cool recovery from cardiac arrest Vol.3:Organ regeneration research leaps forward Vol.4:Cardiac mechanosensitive integrator Vol.5:Cell injections get to the heart of congenital defects Vol.6:Fourth key molecule identified in bone development Vol.7:Anticancer virus solution provides an alternative to surgery Vol.8:Light responsive dye stimulates sight in genetically blind patients Vol.9:Diabetes drug helps towards immunity against cancer Vol.10:Enzyme inhibitors treat drug resistant epilepsy Vol.11:Compound protein combination shows promise for arthritis treatment Vol.12:Molecular features of the circadian clock system in fruit flies Vol.13:Peptide directs artificial tissue growth Vol.14:Simplified boron compound may treat brain tumours Vol.15:Metamaterial absorbers for infrared inspection technologies Vol.16:Epigenetics research traces how crickets restore lost limbs Vol.17:Cell research shows pathway for suppressing hepatitis B virus Vol.18:Therapeutic protein targets liver disease Vol.19:Study links signalling protein to osteoarthritis Tsushima-naka, Kita-ku, Okayama Japan
4 Vol.20:Lack of enzyme promotes fatty liver disease in thin patients Vol.21:Combined gene transduction and light therapy targets gastric cancer Vol.22:Medical supportive device for hemodialysis catheter puncture Vol.23:Development of low cost oral inactivated vaccines for dysentery Vol.24:Sticky molecules to tackle obesity and diabetes Vol.25:Self administered aroma foot massage may reduce symptoms of anxiety Vol.26:Protein for preventing heart failure Vol.27:Keeping cells in shape to fight sepsis Vol.28:Viral based therapy for bone cancer Vol.29:Photoreactive compound allows protein synthesis control with light Vol.30:Cancer stem cells role in tumor growth revealed Vol.31:Prevention of RNA virus replication Vol.32:Enzyme target for slowing bladder cancer invasion Vol.33:Attacking tumors from the inside Vol.34:Novel mouse model for studying pancreatic cancer Vol.35:Potential cause of Lafora disease revealed Vol.36:Overloading of protein localization triggers cellular defects Vol.37:Protein dosage compensation mechanism unravelled Vol.38:Bioengineered tooth restoration in a large mammal Vol.39:Successful test of retinal prosthesis implanted in rats Vol.40:Antibodies prolong seizure latency in epileptic mice Vol.41:Inorganic biomaterials for soft tissue adhesion Vol.42:Potential drug for treating chronic pain with few side effects Vol.43:Potential origin of cancer associated cells revealed Vol.44:Protection from plant extracts Vol.45:Link between biological clock disturbance and brain dysfunction uncovered Vol.46:New method for suppressing lung cancer oncogene Vol.47:Candidate genes for eye misalignment identified Vol.48:Nanotechnology based approach to cancer virotherapy Vol.49:Cell membrane as material for bone formation Vol.50:Iron removal as a potential cancer therapy Vol.51:Potential of 3D nanoenvironments for experimental cancer Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration Vol.54:Measuring ion concentration in solutions for clinical and environmental research Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis Vol.56:New device for assisting accurate hemodialysis catheter placement Vol.57:Possible link between excess chewing muscle activity and dental disease Vol.58:Insights into mechanisms governing the resistance to the anti cancer medication cetuximab Vol.59:Role of commensal flora in periodontal immune response investigated Vol.60:Role of commensal microbiota in bone remodeling Tsushima-naka, Kita-ku, Okayama Japan
5 Vol.61:Mechanical stress affects normal bone development Vol.62:3D tissue model offers insights into treating pancreatic cancer Vol.63:Promising biomarker for vascular disease relapse revealed Vol.64:Inflammation in the brain enhances the side effects of hypnotic medication Vol.65:Game changer: How do bacteria play Tag? Okayama University (Tsushima Campus, Okayama City) u.ac.jp/eng/access_maps/tsushima_campus.html Pergola Kazuyo Sejima + Ryue Nishizawa / SANAA Okayama University (Tsushima Campus, Okayama City) u.ac.jp/eng/access_maps/tsushima_campus.html Tsushima-naka, Kita-ku, Okayama Japan
6 About Okayama University Okayama University is one of the largest comprehensive universities in Japan with roots going back to the Medical Training Place sponsored by the Lord of Okayama and established in Now with 1,300 faculty and 13,000 students, the University offers courses in specialties ranging from medicine and pharmacy to humanities and physical sciences. Okayama University is located in the heart of Japan approximately 3 hours west of Tokyo by Shinkansen. Website: Hirofumi Makino, M.D., Ph.D. President, Okayama University Okayama University supports the Sustainable Development Goals Tsushima-naka, Kita-ku, Okayama Japan
Source: Okayama University (JAPAN), Public Relations and Information Strategy
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