| Summary: | Retinal mitochondria are damaged in diabetes-accelerating apoptosis of capillary cells, and ultimately, leading to degenerative capillaries. Diabetes also upregulates many long noncoding RNAs (LncRNAs), including Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i>. These RNAs have more than 200 nucleotides and no open reading frame for translation. Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> are encoded by nuclear genome, but nuclear-encoded LncRNAs can also translocate in the mitochondria. Our aim was to investigate the role of Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> in mitochondrial homeostasis. Using human retinal endothelial cells, the effect of high glucose on Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial localization was examined by RNA fluorescence in situ hybridization. The role of these LncRNAs in mitochondrial membrane potential (by JC-I staining), mtDNA integrity (by extended length PCR) and in protective mtDNA nucleoids (by SYBR green staining) was examined in <i>MALAT1-</i> or <i>NEAT1-siRNA</i> transfected cells. High glucose increased Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial expression, and <i>MALAT1</i>-siRNA or <i>NEAT1</i>-siRNA ameliorated glucose-induced damage to mitochondrial membrane potential and mtDNA, and prevented decrease in mtDNA nucleoids. Thus, increased mitochondrial translocation of Lnc<i>MALAT1</i> or Lnc<i>NEAT1</i> in a hyperglycemic milieu plays a major role in damaging the mitochondrial structural and genomic integrity. Regulation of these LncRNAs can protect mitochondrial homeostasis, and ameliorate formation of degenerative capillaries in diabetic retinopathy.
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