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PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling.

Jones, AW; Yao, Z; Vicencio, JM; Karkucinska-Wieckowska, A; Szabadkai, G; (2012) PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling. Mitochondrion , 12 (1) 86 - 99. 10.1016/j.mito.2011.09.009. Green open access

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Abstract

Over the past two decades, a complex nuclear transcriptional machinery controlling mitochondrial biogenesis and function has been described. Central to this network are the PGC-1 family coactivators, characterised as master regulators of mitochondrial biogenesis. Recent literature has identified a broader role for PGC-1 coactivators in both cell death and cellular adaptation under conditions of stress, here reviewed in the context of the pathology associated with cancer, neurodegeneration and cardiovascular disease. Moreover, we propose that these studies also imply a novel conceptual framework on the general role of mitochondrial dysfunction in disease. It is now well established that the complex nuclear transcriptional control of mitochondrial biogenesis allows for adaptation of mitochondrial mass and function to environmental conditions. On the other hand, it has also been suggested that mitochondria alter their function according to prevailing cellular energetic requirements and thus function as sensors that generate signals to adjust fundamental cellular processes through a retrograde mitochondria-nucleus signalling pathway. Therefore, altered mitochondrial function can affect cell fate not only directly by modifying cellular energy levels or redox state, but also indirectly, by altering nuclear transcriptional patterns. The current literature on such retrograde signalling in both yeast and mammalian cells is thus reviewed, with an outlook on its potential contribution to disease through the regulation of PGC-1 family coactivators. We propose that further investigation of these pathways will lead to the identification of novel pharmacological targets and treatment strategies to combat disease.

Type: Article
Title: PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling.
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.mito.2011.09.009
Publisher version: http://dx.doi.org/10.1016/j.mito.2011.09.009
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Cardiovascular Diseases, Gene Expression Regulation, Humans, Mitochondria, Neoplasms, Neurodegenerative Diseases, Stress, Physiological, Transcription Factors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/1330549
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