| First Author | Martin OJ | Year | 2014 |
| Journal | Circ Res | Volume | 114 |
| Issue | 4 | Pages | 626-36 |
| PubMed ID | 24366168 | Mgi Jnum | J:223702 |
| Mgi Id | MGI:5660089 | Doi | 10.1161/CIRCRESAHA.114.302562 |
| Citation | Martin OJ, et al. (2014) A role for peroxisome proliferator-activated receptor gamma coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res 114(4):626-36 |
| abstractText | 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 gamma coactivator-1 (PGC-1) alpha and PGC-1beta, 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-1alpha/beta-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-1alpha/beta-deficient mice. PGC-lalpha was shown to directly regulate Mfn1 gene transcription by coactivating the estrogen-related receptor alpha on a conserved DNA element. Surprisingly, PGC-1alpha/beta 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. |
