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Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.

Publication ,  Journal Article
Burkewitz, K; Morantte, I; Weir, HJM; Yeo, R; Zhang, Y; Huynh, FK; Ilkayeva, OR; Hirschey, MD; Grant, AR; Mair, WB
Published in: Cell
February 26, 2015

Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 26, 2015

Volume

160

Issue

5

Start / End Page

842 / 855

Location

United States

Related Subject Headings

  • Trans-Activators
  • Signal Transduction
  • Receptors, Cytoplasmic and Nuclear
  • Neurons
  • Mitochondria
  • Longevity
  • Developmental Biology
  • Cyclic AMP Response Element-Binding Protein
  • Catecholamines
  • Caenorhabditis elegans Proteins
 

Citation

APA
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ICMJE
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Burkewitz, K., Morantte, I., Weir, H. J. M., Yeo, R., Zhang, Y., Huynh, F. K., … Mair, W. B. (2015). Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell, 160(5), 842–855. https://doi.org/10.1016/j.cell.2015.02.004
Burkewitz, Kristopher, Ianessa Morantte, Heather J. M. Weir, Robin Yeo, Yue Zhang, Frank K. Huynh, Olga R. Ilkayeva, Matthew D. Hirschey, Ana R. Grant, and William B. Mair. “Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.Cell 160, no. 5 (February 26, 2015): 842–55. https://doi.org/10.1016/j.cell.2015.02.004.
Burkewitz K, Morantte I, Weir HJM, Yeo R, Zhang Y, Huynh FK, et al. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell. 2015 Feb 26;160(5):842–55.
Burkewitz, Kristopher, et al. “Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.Cell, vol. 160, no. 5, Feb. 2015, pp. 842–55. Pubmed, doi:10.1016/j.cell.2015.02.004.
Burkewitz K, Morantte I, Weir HJM, Yeo R, Zhang Y, Huynh FK, Ilkayeva OR, Hirschey MD, Grant AR, Mair WB. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell. 2015 Feb 26;160(5):842–855.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 26, 2015

Volume

160

Issue

5

Start / End Page

842 / 855

Location

United States

Related Subject Headings

  • Trans-Activators
  • Signal Transduction
  • Receptors, Cytoplasmic and Nuclear
  • Neurons
  • Mitochondria
  • Longevity
  • Developmental Biology
  • Cyclic AMP Response Element-Binding Protein
  • Catecholamines
  • Caenorhabditis elegans Proteins