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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.CircR

Abstract

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.

Authors+Show Affiliations

From the Diabetes and Obesity Research Center, Cardiovascular Pathobiology Program, Sanford-Burnham Medical Research Institute, Orlando, FL (O.J.M., L.L., M.M.S., T.C.L., D.P.K.); Institute for Research in Biomedicine, Barcelona, Spain (A.Z.); Department de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain (A.Z.); CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Spain (A.Z.); Department of Biochemistry, University of Wisconsin-Madison, WI (M.P.K., A.D.A.); and Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (D.M.M.).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24366168

Citation

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." Circulation Research, vol. 114, no. 4, 2014, pp. 626-36.
Martin OJ, Lai L, Soundarapandian MM, 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;114(4):626-36.
Martin, O. J., Lai, L., Soundarapandian, M. M., Leone, T. C., Zorzano, A., Keller, M. P., Attie, A. D., Muoio, D. M., & Kelly, D. P. (2014). A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circulation Research, 114(4), 626-36. https://doi.org/10.1161/CIRCRESAHA.114.302562
Martin OJ, 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. PubMed PMID: 24366168.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. AU - Martin,Ola J, AU - Lai,Ling, AU - Soundarapandian,Mangala M, AU - Leone,Teresa C, AU - Zorzano,Antonio, AU - Keller,Mark P, AU - Attie,Alan D, AU - Muoio,Deborah M, AU - Kelly,Daniel P, Y1 - 2013/12/23/ PY - 2013/12/25/entrez PY - 2013/12/25/pubmed PY - 2014/4/22/medline KW - Mfn1 protein, human KW - cardiomyopathies KW - mitochondrial dynamics SP - 626 EP - 36 JF - Circulation research JO - Circ. Res. VL - 114 IS - 4 N2 - 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. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/24366168/A_role_for_peroxisome_proliferator_activated_receptor_γ_coactivator_1_in_the_control_of_mitochondrial_dynamics_during_postnatal_cardiac_growth_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.114.302562?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -