한빛사논문
- 조회3,256
Abstract
Hyun-Eui Kim1, Ana Rodrigues Grant2, Milos S. Simic1, Rebecca A. Kohnz3, Daniel K. Nomura3, 4, Jenni Durieux1, Celine E. Riera1, Melissa Sanchez1, Erik Kapernick1, 5, Suzanne Wolff1, Andrew Dillin1, 6
1 Glenn Center for Research on Aging, Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
2 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
3 Departments of Chemistry and Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
4 Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA
5 Present address: Los Angeles College of Music, Pasadena, CA 91105, USA
6 Lead Contact
Corresponding author : Andrew Dillin
Summary
Defects in mitochondrial metabolism have been increasingly linked with age-onset protein-misfolding diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. In response to protein-folding stress, compartment-specific unfolded protein responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small-molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.
논문정보
- Research article
- 2016년 09월 (BRIC 등록일 2016-09-13)
- 국외 연구진
- 생명과학 > 세포생물학
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