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Citation
Dorn, G.W., Clark, C.F., Eschenbacher, W.H., Kang, M.Y., Engelhard, J.T., Warner, S.J., Matkovich, S.J., Jowdy, C.C. (2011). MARF and Opa1 Control Mitochondrial and Cardiac Function in Drosophila.  Circulation Res. 108(1): 12--17.
FlyBase ID
FBrf0212708
Publication Type
Research paper
Abstract

Mitochondria interact via actions of outer and inner membrane fusion proteins. The role of mitochondrial fusion in functioning of the heart, where mitochondria comprise ≈30% of cardiomyocyte volume and their intermyofilament spatial arrangement with other mitochondria is highly ordered, is unknown.Model and analyze mitochondrial fusion defects in Drosophila melanogaster heart tubes with tincΔ4Gal4-directed expression of RNA interference (RNAi) for mitochondrial assembly regulatory factor (MARF) and optic atrophy (Opa)1.Live imaging analysis revealed that heart tube-specific knockdown of MARF or Opa1 increases mitochondrial morphometric heterogeneity and induces heart tube dilation with profound contractile impairment. Sarcoplasmic reticular structure was unaffected. Cardiomyocyte expression of human mitofusin (mfn)1 or -2 rescued MARF RNAi cardiomyopathy, demonstrating functional homology between Drosophila MARF and human mitofusins. Suppressing mitochondrial fusion increased compensatory expression of nuclear-encoded mitochondrial genes, indicating mitochondrial biogenesis. The MARF RNAi cardiomyopathy was prevented by transgenic expression of superoxide dismutase 1.Mitochondrial fusion is essential to cardiomyocyte mitochondrial function and regeneration. Reactive oxygen species are key mediators of cardiomyopathy in mitochondrial fusion-defective cardiomyocytes. Postulated mitochondrial-endoplasmic reticulum interactions mediated uniquely by mfn2 appear dispensable to functioning of the fly heart.

PubMed ID
PubMed Central ID
PMC3337031 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Circulation Res.
    Title
    Circulation Research
    Publication Year
    1953-
    ISBN/ISSN
    0009-7330
    Data From Reference