Mitochondrial dysfunction is a primary consequence of nearly all age-onset neurodegenerative diseases, and can be the consequence of exposure to even mild levels of a wide-range of environmental toxins. Surprisingly, the applicant's lab has uncovered that mitochondrial stress in one cell type can be communicated to a distal cell type that has not undergone mitochondrial stress. Using issue specific promoters in the nematode C. elegans that drive expression of dsRNA of a subunit of complex IV of the ETC in the nervous system, it has been shown that neuronal mitochondrial stress can be communicated to distal cells, such as the intestine. The ability of the nervous system to communicate this mild stress results in increased longevity and survival of the entire animal. The goal of the proposed studies is to identify the source and nature of this signaling mechanism.
We have discovered that mitochondria from one cell can communicate to cells at a distance. This communication is initiated in the nervous system and ensures the survival of an animal under conditions of stress. The identity of the language in which these cells communicate will provide new avenues of therapy for people that suffer from diseases associated with mitochondrial malfunction, such as stroke, Alzheimer's, Parkinson's, Huntington's, diabetes and rare metabolic diseases. !
|Merkwirth, Carsten; Jovaisaite, Virginija; Durieux, Jenni et al. (2016) Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity. Cell 165:1209-1223|
|Kim, Hyun-Eui; Grant, Ana Rodrigues; Simic, Milos S et al. (2016) Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response. Cell 166:1539-1552.e16|
|Heimbucher, Thomas; Liu, Zheng; Bossard, Carine et al. (2015) The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity. Cell Metab 22:151-63|
|Wilkinson, Deepti S; Jariwala, Jinel S; Anderson, Ericka et al. (2015) Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Mol Cell 57:55-68|
|Douglas, Peter M; Baird, Nathan A; Simic, Milos S et al. (2015) Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity. Cell Rep 12:1196-1204|
|Schinzel, Robert; Dillin, Andrew (2015) Endocrine aspects of organelle stress—cell non-autonomous signaling of mitochondria and the ER. Curr Opin Cell Biol 33:102-10|
|Dillin, Andrew (2014) Profile of Kazutoshi Mori and Peter Walter, 2014 Lasker Basic Medical Research awardees: The unfolded protein response. Proc Natl Acad Sci U S A 111:17696-7|
|Carrano, Andrea C; Dillin, Andrew; Hunter, Tony (2014) A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans. Nat Commun 5:3772|
|Wolff, Suzanne; Weissman, Jonathan S; Dillin, Andrew (2014) Differential scales of protein quality control. Cell 157:52-64|
|Patti, Gary J; Tautenhahn, Ralf; Johannsen, Darcy et al. (2014) Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension. Metabolomics 10:737-743|
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