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

Published

Journal Article

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.Our aim was to assess the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts in mice.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.These results reveal distinct developmental stage-specific programs involved in cardiac mitochondrial dynamics.

Full Text

Duke Authors

Cited Authors

  • Martin, OJ; Lai, L; Soundarapandian, MM; Leone, TC; Zorzano, A; Keller, MP; Attie, AD; Muoio, DM; Kelly, DP

Published Date

  • February 2014

Published In

Volume / Issue

  • 114 / 4

Start / End Page

  • 626 - 636

PubMed ID

  • 24366168

Pubmed Central ID

  • 24366168

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

International Standard Serial Number (ISSN)

  • 0009-7330

Digital Object Identifier (DOI)

  • 10.1161/CIRCRESAHA.114.302562

Language

  • eng