Impact Factor


Front. Physiol., 17 May 2012 | http://dx.doi.org/10.3389/fphys.2012.00139

The yeast retrograde response as a model of intracellular signaling of mitochondrial dysfunction

  • 1 Department of Medicine, Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA
  • 2 School of Biomedical Engineering, Drexel University, Philadelphia, PA, USA

Mitochondrial dysfunction activates intracellular signaling pathways that impact yeast longevity, and the best known of these pathways is the retrograde response. More recently, similar responses have been discerned in other systems, from invertebrates to human cells. However, the identity of the signal transducers is either unknown or apparently diverse, contrasting with the well-established signaling module of the yeast retrograde response. On the other hand, it has become equally clear that several other pathways and processes interact with the retrograde response, embedding it in a network responsive to a variety of cellular states. An examination of this network supports the notion that the master regulator NFκB aggregated a variety of mitochondria-related cellular responses at some point in evolution and has become the retrograde transcription factor. This has significant consequences for how we view some of the deficits associated with aging, such as inflammation. The support for NFκB as the retrograde response transcription factor is not only based on functional analyses. It is bolstered by the fact that NFκB can regulate Myc–Max, which is activated in human cells with dysfunctional mitochondria and impacts cellular metabolism. Myc–Max is homologous to the yeast retrograde response transcription factor Rtg1–Rtg3. Further research will be needed to disentangle the pro-aging from the anti-aging effects of NFκB. Interestingly, this is also a challenge for the complete understanding of the yeast retrograde response.

Keywords: retrograde response, RTG genes, NFκB, metabolism, stress, mitophagy, Saccharomyces cerevisiae, replicative lifespan

Citation: Jazwinski SM and Kriete A (2012) The yeast retrograde response as a model of intracellular signaling of mitochondrial dysfunction. Front. Physio. 3:139. doi: 10.3389/fphys.2012.00139

Received: 30 March 2012; Accepted: 26 April 2012;
Published online: 17 May 2012.

Edited by:

Vladimir Titorenko, Concordia University, Canada

Reviewed by:

Christopher Baines, University of Missouri–Columbia, USA
Mildred Audrey Pointer, North Carolina Central University, USA

Copyright: © 2012 Jazwinski and Kriete. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: S. Michal Jazwinski, Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-12, New Orleans, LA 70112, USA. e-mail: sjazwins@tulane.edu