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A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.

Publication ,  Journal Article
Martin, OJ; Lai, L; Soundarapandian, MM; Leone, TC; Zorzano, A; Keller, MP; Attie, AD; Muoio, DM; Kelly, DP
Published in: Circ Res
February 14, 2014

RATIONALE: Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) α and PGC-1β, have been shown to regulate mitochondrial biogenesis in the heart at the time of birth. The function of PGC-1 coactivators in the heart after birth has been incompletely understood. OBJECTIVE: Our aim was to assess the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts in mice. METHODS AND RESULTS: Conditional gene targeting was used in mice to explore the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts. Marked mitochondrial structural derangements were observed in hearts of PGC-1α/β-deficient mice during postnatal growth, including fragmentation and elongation, associated with the development of a lethal cardiomyopathy. The expression of genes involved in mitochondrial fusion (Mfn1, Opa1) and fission (Drp1, Fis1) was altered in the hearts of PGC-1α/β-deficient mice. PGC-lα was shown to directly regulate Mfn1 gene transcription by coactivating the estrogen-related receptor α on a conserved DNA element. Surprisingly, PGC-1α/β deficiency in the adult heart did not result in evidence of abnormal mitochondrial dynamics or heart failure. However, transcriptional profiling demonstrated that PGC-1 coactivators are required for high-level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial dynamics and energy transduction in the adult heart. CONCLUSIONS: These results reveal distinct developmental stage-specific programs involved in cardiac mitochondrial dynamics.

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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

February 14, 2014

Volume

114

Issue

4

Start / End Page

626 / 636

Location

United States

Related Subject Headings

  • Transcription Factors
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Mitochondria, Heart
  • Mice, Knockout
  • Mice
  • Male
  • Heart
  • Gene Expression Regulation, Developmental
  • GTP Phosphohydrolases
  • Female
 

Citation

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Martin, O. J., Lai, L., Soundarapandian, M. M., Leone, T. C., Zorzano, A., Keller, M. P., … Kelly, D. P. (2014). A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res, 114(4), 626–636. https://doi.org/10.1161/CIRCRESAHA.114.302562
Martin, Ola J., Ling Lai, Mangala M. Soundarapandian, Teresa C. Leone, Antonio Zorzano, Mark P. Keller, Alan D. Attie, Deborah M. Muoio, and Daniel P. Kelly. “A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.Circ Res 114, no. 4 (February 14, 2014): 626–36. https://doi.org/10.1161/CIRCRESAHA.114.302562.
Martin OJ, Lai L, Soundarapandian MM, Leone TC, Zorzano A, Keller MP, et al. A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res. 2014 Feb 14;114(4):626–36.
Martin, Ola J., et al. “A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.Circ Res, vol. 114, no. 4, Feb. 2014, pp. 626–36. Pubmed, doi:10.1161/CIRCRESAHA.114.302562.
Martin OJ, Lai L, Soundarapandian MM, Leone TC, Zorzano A, Keller MP, Attie AD, Muoio DM, Kelly DP. A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res. 2014 Feb 14;114(4):626–636.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

February 14, 2014

Volume

114

Issue

4

Start / End Page

626 / 636

Location

United States

Related Subject Headings

  • Transcription Factors
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Mitochondria, Heart
  • Mice, Knockout
  • Mice
  • Male
  • Heart
  • Gene Expression Regulation, Developmental
  • GTP Phosphohydrolases
  • Female