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Translational regulation of the mitochondrial genome following redistribution of mitochondrial microRNA (MitomiR) in the diabetic heart.
Author(s) -
Jagannathan Rajaganapathi,
Thapa Dharendra,
Baseler Walter A,
Shepherd Danielle L,
Croston Tara L,
Nichols Cody E,
Lewis Sara E,
Hollander John M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.701.10
Subject(s) - mitochondrion , biology , mitochondrial dna , microbiology and biotechnology , genome , genetics , gene
Cardiomyocytes contain mitochondria that are situated in distinct subcellular regions, termed subsarcolemmal mitochondria (SSM), and interfibrillar mitochondria (IFM). We have identified a functional pool of mitochondrial microRNAs (mitomiRs) that are redistributed in spatially‐distinct mitochondrial subpopulations in response to diabetic mellitus. We observed an inverse distribution pattern between SSM and IFM following diabetic insult such that greater than 54% of identified mitomiRs were inversely distributed between the two subpopulations. Specific tri‐nucleotide sequence motifs (UGG and AGG) were observed in the seeding region of identified mitomiRs which may be predictive for distribution in the mitochondrion. Redistributed mitomiRs displayed interactions with the mitochondrial genome requiring association with RISC proteins (AGO2 and FXR1) for translational regulation. Redistribution of mitomiR‐378 to the IFM following type 1 diabetic insult led to a down regulation of mitochondrially‐encoded F0 components ATP6 and ATP8. We propose that mitomiR translational regulation of mitochondrially‐encoded proteins oscillates in mitochondrial subpopulations in response to type 1 diabetic insult, suggesting a dynamic system that can regulate the mitochondrial genome during pathological states in a spatiallydistinct manner.(Support: NIH DP2DK083095, NIH T32HL090610, DGE‐1144676)