Article
Biotechnology & Applied Microbiology
Yeping Lin, Yunzi Feng, Lin Zheng, Mouming Zhao, Mingtao Huang
Summary: This study focuses on the yeast Saccharomyces cerevisiae and its potential for increased protein production through genetic engineering. By targeting genes related to protein synthesis and using transcriptome analysis and physiological characterizations, key regulatory and metabolic network changes were identified. It was found that manipulating genes relevant to stress response in protein synthesis significantly increased protein secretion. The genetic modifications identified in this study provide valuable targets for constructing efficient yeast cell factories for protein production.
METABOLIC ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Huong Thi Phuong, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: Upon ER stress, cells initiate the unfolded protein response (UPR) through Ire1. This study investigates how the accumulation of misfolded transmembrane proteins in the ER induces UPR. The authors find that GFP-tagged Ire1 co-localizes with aggregated Pma1-2308-mCherry on the ER membrane. A specific point mutation in Ire1 impairs its activation upon lipid bilayer stress (LBS), compromising the co-localization and UPR induced by Pma1-2308-mCherry. The study suggests that Pma1-2308-mCherry affects the properties of the ER membrane at aggregation sites, leading to Ire1 recruitment, self-association, and activation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Phuong Thi Mai Nguyen, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: The unfolded protein response (UPR) is a cellular response to deal with the accumulation of unfolded proteins in the endoplasmic reticulum (ER). This study demonstrates that constitutive induction of UPR in nonstress conditions leads to growth retardation, which can be partially rescued by weak ER stress. Additionally, the stable expression of ER-localized GFP in UPR-induced cells enhances UPR activity and promotes the production of triglycerides and heterogenous carotenoids. These findings have implications for metabolic engineering and the production of valuable lipidic molecules.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Juan Facundo Gulias, Florencia Niesi, Martin Aran, Susana Correa-Garcia, Mariana Bermudez-Moretti
Summary: Aging is a gradual decline in physiological integrity, which impairs functionality and increases mortality susceptibility. Dietary restriction, a known intervention to slow down aging, mimics nutrient scarcity without causing malnutrition. This study investigated the role of the transcription factor Gcn4 in the aging process of S. cerevisiae cells. The absence of Gcn4 led to various physiological changes, including increased mitochondrial activity and reactive oxygen species accumulation. Additionally, the mutant cells exhibited reduced ethanol production and lower levels of trehalose and free amino acids, disrupting cellular homeostasis and ultimately leading to a shortened lifespan.
Article
Multidisciplinary Sciences
Manuel Hotz, Nathaniel H. Thayer, David G. Hendrickson, Elizabeth L. Schinski, Jun Xu, Daniel E. Gottschling
Summary: This study discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene and the replicative lifespan in budding yeast. The data suggest that regulatory mechanisms involving ribosomal DNA copy number limit lifespan and changes in rDNA copy number might explain the effects of lifespan-enhancing mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Rohan Dandage, Caroline M. Berger, Isabelle Gagnon-Arsenault, Kyung-Mee Moon, Richard Greg Stacey, Leonard J. Foster, Christian R. Landry
Summary: The study investigated protein-protein interactions in hybrids between yeast species, finding that most interactions are similar to those of the parents but with some altered instances. It suggests that the occurrence of chimeric protein complexes is frequent, potentially due to incompatibilities or imbalances between parental proteomes.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biology
David M. Garcia, Edgar A. Campbell, Christopher M. Jakobson, Mitsuhiro Tsuchiya, Ethan A. Shaw, Acadia L. DiNardo, Matt Kaeberlein, Daniel F. Jarosz
Summary: This study reveals a natural example of how the interplay between growth and lifespan can be epigenetically controlled through a RNA-modifying enzyme acting as a prion in yeast cells, leading to increased proliferation rates but shortened lifespan. The epigenetic state, [B/G(+)], allows cells to heritably alter their translational program, resulting in differential synthesis of proteins that regulate proliferation and aging.
Article
Biology
Brooke Zanco, Christen K. Mirth, Carla M. Sgro, Matthew D. W. Piper
Summary: Research on fruit flies shows that the influence of protein and carbohydrates on lifespan is indirect, affecting the distribution of dietary sterols. Supplementing with cholesterol can rescue the shortened lifespan caused by high protein: carbohydrate diets. This highlights the complex and indirect effects of nutrient-dependent trade-offs on life histories.
Article
Cell Biology
Arman Ali Shah, Binghua Liu, Zhihuai Tang, Wang Wang, Wenjie Yang, Quanjun Hu, Yan Liu, Nianhui Zhang, Ke Liu
Summary: This study demonstrates that short-term treatment with fast H2S releasing donor NaHS at 96 hours after inoculation extends yeast lifespan, while treatments before 72 hours fail to do so. Early and late H2S treatments have similar effects on pathways related to lifespan regulation, but early treatment leads to unstable expression of antioxidant genes. Differences in gene regulation are also observed between early and late H2S treatment.
Article
Cell Biology
Nan Xin, Jenni Durieux, Chunxia Yang, Suzanne Wolff, Hyun-Eui Kim, Andrew Dillin
Summary: The mitochondrial unfolded protein response (UPRmt) maintains mitochondrial proteostasis by regulating the transcription factor ATFS-1. After UPRmt activation, ATFS-1 enters the nucleus to regulate UPRmt genes. The study found that despite reduced mitochondrial membrane potential, mitochondrial import increases during UPRmt activation, and an intact import machinery is essential for UPRmt-mediated lifespan extension.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Praveen K. Patnaik, Carine Beaupere, Hanna Barlit, Antonia Maria Romero, Mitsuhiro Tsuchiya, Michael Muir, Maria Teresa Martinez-Pastor, Sergi Puig, Matt Kaeberlein, Vyacheslav M. Labunskyy
Summary: This study reveals that defects in the mRNA-binding protein Cth2 contribute to iron dys-homeostasis, aging, and lifespan regulation in yeast. Modulation of Cth2 activity can impact mitochondrial function and extend lifespan.
Review
Neurosciences
Lei Wang, Laura Bianchi
Summary: Mounting evidence supports the key role of glia in organismal ageing, with neuropeptides released by glia acting long distance to regulate ageing and activate the unfolded protein response (UPR) in C. elegans. This cell-nonautonomous activation of UPR leads to extension of lifespan, suggesting potential for novel anti-ageing therapies.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Jovian Lin Jing, Trishia Cheng Yi Ning, Federica Natali, Frank Eisenhaber, Mohammad Alfatah
Summary: Aging is a global challenge, but iron supplementation can delay aging and increase cellular lifespan by upregulating mitochondrial genes and increasing ATP levels. Additionally, iron supplementation has anti-aging effects in AMPK knockout mutants. Thus, iron supplementation has potential therapeutic applications for delaying aging and prolonging healthy lifespan.
Article
Biochemistry & Molecular Biology
Yuki Ishiwata-Kimata, Tatsuya Hata, Yukio Kimata
Summary: This study investigated the activity of Ire1 under ER stress and found that only the clustered form of Ire1 induced UPR, while the dimerized form was almost inactive when Ire1 was tagged with irrelevant peptides at the C terminus. This finding reveals a fundamental difference between the dimeric and clustered forms of Ire1.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Article
Oncology
Ankit Patel, Masanori Oshi, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Summary: The study found a correlation between the unfolded protein response (UPR) and hepatocellular carcinoma (HCC) in terms of carcinogenesis, cancer progression, and patient survival. The UPR score can serve as a biomarker for predicting cancer progression and patient prognosis in HCC.
Article
Cell Biology
Mark A. McCormick, Joe R. Delaney, Mitsuhiro Tsuchiya, Scott Tsuchiyama, Anna Shemorry, Sylvia Sim, Annie Chia-Zong Chou, Umema Ahmed, Daniel Carr, Christopher J. Murakami, Jennifer Schleit, George L. Sutphin, Brian M. Wasko, Christopher F. Bennett, Adrienne M. Wang, Brady Olsen, Richard P. Beyer, Theodor K. Bammler, Donna Prunkard, Simon C. Johnson, Juniper K. Pennypacker, Elroy An, Arieanna Anies, Anthony S. Castanza, Eunice Choi, Nick Dang, Shiena Enerio, Marissa Fletcher, Lindsay Fox, Sarani Goswami, Sean A. Higgins, Molly A. Holmberg, Di Hu, Jessica Hui, Monika Jelic, Ki-Soo Jeong, Elijah Johnston, Emily O. Kerr, Jin Kim, Diana Kim, Katie Kirkland, Shannon Klum, Soumya Kotireddy, Eric Liao, Michael Lim, Michael S. Lin, Winston C. Lo, Dan Lockshon, Hillary A. Miller, Richard M. Moller, Brian Muller, Jonathan Oakes, Diana N. Pak, Zhao Jun Peng, Kim M. Pham, Tom G. Pollard, Prarthana Pradeep, Dillon Pruett, Dilreet Rai, Brett Robison, Ariana A. Rodriguez, Bopharoth Ros, Michael Sage, Manpreet K. Singh, Erica D. Smith, Katie Snead, Amrita Solanky, Benjamin L. Spector, Kristan K. Steffen, Bie Nga Tchao, Marc K. Ting, Helen Vander Wende, Dennis Wang, K. Linnea Welton, Eric A. Westman, Rachel B. Brem, Xin-guang Liu, Yousin Suh, Zhongjun Zhou, Matt Kaeberlein, Brian K. Kennedy
Article
Cell Biology
Payel Sen, Weiwei Dang, Greg Donahue, Junbiao Dai, Jean Dorsey, Xiaohua Cao, Wei Liu, Kajia Cao, Rocco Perry, Jun Yeop Lee, Brian M. Wasko, Daniel T. Carr, Chong He, Brett Robison, John Wagner, Brian D. Gregory, Matt Kaeberlein, Brian K. Kennedy, Jef D. Boeke, Shelley L. Berger
GENES & DEVELOPMENT
(2015)
Article
Multidisciplinary Sciences
Gholamali Jafari, Brian M. Wasko, Ashley Tonge, Nathan Schurman, Cindy Dong, Zhongyu Li, Rebecca Peters, Ernst-Bernhard Kayser, Jason N. Pitt, Phil G. Morgan, Margaret M. Sedensky, Antony R. Crofts, Matt Kaeberlein
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Cell Biology
Anna B. Sunshine, Giang T. Ong, Daniel P. Nickerson, Daniel Carr, Christopher J. Murakami, Brian M. Wasko, Anna Shemorry, Alexey J. Merz, Matt Kaeberlein, Maitreya J. Dunham
Article
Cell Biology
Carine Beaupere, Brian M. Wasko, Jared Lorusso, Brian K. Kennedy, Matt Kaeberlein, Vyacheslav M. Labunskyy
Article
Genetics & Heredity
Christopher F. Bennett, Jane J. Kwon, Christine Chen, Joshua Russell, Kathlyn Acosta, Nikolay Burnaevskiy, Matthew M. Crane, Alessandro Bitto, Helen Vander Wende, Marissa Simko, Victor Pineda, Ryan Rossner, Brian M. Wasko, Haeri Choi, Shiwen Chen, Shirley Park, Gholamali Jafari, Bryan Sands, Carissa Perez Olsen, Alexander R. Mendenhall, Philip G. Morgan, Matt Kaeberlein
Review
Biotechnology & Applied Microbiology
Brian M. Wasko, Matt Kaeberlein
FEMS YEAST RESEARCH
(2014)
Article
Cell Biology
Wei Zhao, Bing Xiong Fang, Yu Jie Niu, Yi Na Liu, Bin Liu, Qi Peng, Jiang Bin Li, Brian M. Wasko, Joseph R. Delaney, Brian K. Kennedy, Yousin Suh, Zhong Jun Zhou, Matt Kaeberlein, Xin Guang Liu
MECHANISMS OF AGEING AND DEVELOPMENT
(2014)
Article
Multidisciplinary Sciences
Carine Beaupere, Leticia Dinatto, Brian M. Wasko, Rosalyn B. Chen, Lauren VanValkenburg, Michael G. Kiflezghi, Mitchell B. Lee, Daniel E. L. Promislow, Weiwei Dang, Matt Kaeberlein, Vyacheslav M. Labunskyy
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Simon C. Johnson, Melana E. Yanos, Ernst-Bernhard Kayser, Albert Quintana, Maya Sangesland, Anthony Castanza, Lauren Uhde, Jessica Hui, Valerie Z. Wall, Arni Gagnidze, Kelly Oh, Brian M. Wasko, Fresnida J. Ramos, Richard D. Palmiter, Peter S. Rabinovitch, Philip G. Morgan, Margaret M. Sedensky, Matt Kaeberlein
Article
Multidisciplinary Sciences
Mitchell B. Lee, Ian T. Dowsett, Daniel T. Carr, Brian M. Wasko, Sarah G. Stanton, Michael S. Chung, Niloufar Ghodsian, Anna Bode, Michael G. Kiflezghi, Priya A. Uppal, Katherine A. Grayden, Yordanos C. Elala, Thao T. Tang, Ngoc H. B. Tran, Thu H. B. Tran, Anh B. Diep, Michael Hope, Daniel E. L. Promislow, Scott R. Kennedy, Matt Kaeberlein, Alan J. Herr
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Geriatrics & Gerontology
Kenneth L. Chen, Toby N. Ven, Matthew M. Crane, Matthew L. C. Brunner, Adrian K. Pun, Kathleen L. Helget, Katherine Brower, Dexter E. Chen, Ha Doan, Justin D. Dillard-Telm, Ellen Huynh, Yen-Chi Feng, Zili Yan, Alexandra Golubeva, Roy A. Hsu, Raheem Knight, Jessie Levin, Vesal Mobasher, Michael Muir, Victor Omokehinde, Corey Screws, Esin Tunali, Rachael K. Tran, Luz Valdez, Edward Yang, Scott R. Kennedy, Alan J. Herr, Matt Kaeberlein, Brian M. Wasko
Article
Biochemistry & Molecular Biology
Caroline Struyfs, Tanne L. Cools, Kaat De Cremer, Belem Sampaio-Marques, Paula Ludovico, Brian M. Wasko, Matt Kaeberlein, Bruno P. A. Cammue, Karin Thevissen
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Multidisciplinary Sciences
Ruofan Yu, Xiaohua Cao, Luyang Sun, Jun-Yi Zhu, Brian M. Wasko, Wei Liu, Emeline Crutcher, Haiying Liu, Myeong Chan Jo, Lidong Qin, Matt Kaeberlein, Zhe Han, Weiwei Dang
Summary: Histone acetylations serve as important epigenetic markers that regulate transcriptional activation in response to metabolic changes and stresses. In this study, the inactivation of the HDA complex was found to activate longevity and confer resistance to stress through trehalose metabolism. This longevity effect is independent of the Cyc8-Tup1 repressor complex and is evolutionarily conserved.
NATURE COMMUNICATIONS
(2021)