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New insights into PGC‐1 coactivators: redefining their role in the regulation of mitochondrial function and beyond

The FEBS journal, 2015-02, Vol.282 (4), p.647-672 [Peer Reviewed Journal]

2014 FEBS ;2014 FEBS. ;ISSN: 1742-464X ;EISSN: 1742-4658 ;DOI: 10.1111/febs.13175 ;PMID: 25495651

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Title:
New insights into PGC‐1 coactivators: redefining their role in the regulation of mitochondrial function and beyond
Author: Villena, Josep A
Subjects: animal models ; Animals ; biogenesis ; Biosynthesis ; diabetes ; energy metabolism ; Energy Metabolism - genetics ; Energy Metabolism - physiology ; Gene expression ; gene expression regulation ; Humans ; mechanism of action ; metabolic disease ; Mice ; Mitochondria - genetics ; Mitochondria - metabolism ; mitochondrial biogenesis ; Mitochondrial Turnover - genetics ; Mitochondrial Turnover - physiology ; neurodegenerative diseases ; OxPhos ; PGC‐1α ; PGC‐1β ; PRC ; Rodents ; Transcription Factors - genetics ; Transcription Factors - metabolism ; transcriptional regulation
Is Part Of: The FEBS journal, 2015-02, Vol.282 (4), p.647-672
Description: Members of the PGC‐1 family of coactivators have been revealed as key players in the regulation of energy metabolism. Early gain‐ and loss‐of‐function studies led to the conclusion that all members of the PGC‐1 family (PGC‐1α, PGC‐1β and PRC) play redundant roles in the control of mitochondrial biogenesis by regulating overlapping gene expression programs. Regardless of this, all PGC‐1 coactivators also appeared to differ in the stimuli to which they respond to promote mitochondrial gene expression. Although PGC‐1α was found to be induced by different physiological or pharmacological cues, PGC‐1β appeared to be unresponsive to such stimuli. Consequently, it has long been widely accepted that PGC‐1α acts as a mediator of mitochondrial biogenesis induced by cues that signal high‐energy needs, whereas the role of PGC‐1β is restricted to the maintenance of basal mitochondrial function. By contrast, the function of PRC appears to be restricted to the regulation of gene expression in proliferating cells. However, recent studies using tissue‐specific mouse models that lack or overexpress different PGC‐1 coactivators have provided emerging evidence not only supporting new roles for PGC‐1s, but also redefining some of the paradigms related to the precise function and mode of action of PGC‐1 coactivators in mitochondrial biogenesis. The present review discusses some of the new findings regarding the control of mitochondrial gene expression by PGC‐1 coactivators in a tissue‐specific context, as well as newly‐uncovered functions of PGC‐1s beyond mitochondrial biogenesis, and their link to pathologies, such as diabetes, muscular dystrophies, neurodegenerative diseases or cancer.
Publisher: England: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies
Language: English
Identifier: ISSN: 1742-464X
EISSN: 1742-4658
DOI: 10.1111/febs.13175
PMID: 25495651
Source: Freely Accessible Journals
MEDLINE

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New insights into PGC‐1 coactivators: redefining their role in the regulation of mitochondrial function and beyond

2014 FEBS ;2014 FEBS. ;ISSN: 1742-464X ;EISSN: 1742-4658 ;DOI: 10.1111/febs.13175 ;PMID: 25495651

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