title: Glutathione S-transferase mediates an ageing response to mitochondrial dysfunction.
abstract: To understand primary mitochondrial disease, we utilized a complex I-deficient Caenorhabditis elegans mutant, gas-1. These animals strongly upregulate the expression of gst-14 (encoding a glutathione S-transferase). Knockdown of gst-14 dramatically extends the lifespan of gas-1 and increases hydroxynonenal (HNE) modified mitochondrial proteins without improving complex I function. We observed no change in reactive oxygen species levels as measured by Mitosox staining, consistent with a potential role of GST-14 in HNE clearance. The upregulation of gst-14 in gas-1 animals is specific to the pharynx. These data suggest that an HNE-mediated response in the pharynx could be beneficial for lifespan extension in the context of complex I dysfunction in C. elegans. Thus, whereas HNE is typically considered damaging, our work is consistent with recent reports of its role in signaling, and that in this case, the signal is pro-longevity in a model of mitochondrial dysfunction.
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. Electronic address: beverley.m.dancy@gmail.com.
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Dancy
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. Electronic address: nicolebrockway9@gmail.com.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brockway
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. Electronic address: renjini@outlook.com.
authors.forename: Renjini
authors.initials: R
authors.lastname: Ramadasan-Nair
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: yyoing@gmail.com.
authors.forename: Yoing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Department of Anesthesiology and Pain Medicine, University of Washington, 1959 NE Pacific Street, BB-1469, Seattle, WA 98195, USA. Electronic address: sedenm@u.washington.edu.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Sedensky
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Department of Anesthesiology and Pain Medicine, University of Washington, 1959 NE Pacific Street, BB-1469, Seattle, WA 98195, USA. Electronic address: philip.morgan@seattlechildrens.org.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Morgan
mesh_terms: D000375:Aging; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004579:Electron Transport; D005982:Glutathione Transferase / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010614:Pharynx / Q000378:metabolism / Q000503:physiopathology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000447:Aldehydes; D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species; C462359:tert-4-hydroxy-2-nonenal; D049452:Green Fluorescent Proteins; D009245:NADH Dehydrogenase; D005982:Glutathione Transferase; C468009:GAS-1 protein, C elegans
keywords: Caenorhabditis elegans; Glutathione S-transferase; Hydroxynonenal; Longevity; Mitochondrial respiratory chain; Reactive oxygen species