The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity
Open accessAbstract
Summary A mild inhibition of mitochondrial respiration extends the lifespan of many organisms, including yeast, worms, flies and mice [1–10], but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly-conserved transcription factor that activates genes that promote survival during hypoxia [11–12]. In this study, we show that inhibiting respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNAi knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended lifespans of clk-1 and isp-1 mutants, which have reduced rates of respiration [1, 4, 13]. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS is increased in respiration mutants, and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.
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Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
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Self-citationGuzy, R. D., & Schumacker, P. T. (2006) · Experimental Physiology · doi:10.1113/expphysiol.2006.033506 · Cited by 881
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Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae
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“Inhibition of respiration is known to trigger a conserved gene expression response called the retrograde response that activates alternative energy pathways and cell protective mechanisms [3, 34].”
Increased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice
Dell'Agnello, C., Leo, S., Agostino, A., Szabadkai, G., Tiveron, C., Zulian, A., Prelle, A., Roubertoux, P., Rizzuto, R., & Zeviani, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl477 · Cited by 308
HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans
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The HIF-1 Hypoxia-Inducible Factor Modulates Lifespan in C. elegans
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Self-citation
Cited by
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel, G. S., & Horvath, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.10.001 · Cited by 1,353
Metadata
- Authors
- Lee, S.-J., Hwang, A. B., & Kenyon, C.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 20
- Issue
- 23
- Pages
- 2131-2136
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1979705609
- Cited by
- 504
- References
- 11
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- bronze
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