MicroRNA ‐382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells

In the current study, microRNA ‐382‐5p was identified as a regulator of mitochondrial biogenesis and dynamics at mRNA levels. Silencing of miRNA‐382‐5p in C2C12 myotubes revealed a collective downregulation of mitochondrial ribosomal proteins and respiratory chain proteins. MiR‐382 silenced C2C12 showed a mitonuclear pr otein imbalance that led to the activation of the mitochondrial unfolded protein response and a reduced basal oxygen consumption rate without affecting mitochondrial content. AbstractProper mitochondrial function plays a central role in cellular metabolism. Various diseases as well as aging are associated with diminished mitochondrial function. Previously, we identified 19 miRNAs putatively involved in the regulation of mitochondrial metabolism in skeletal muscle, a highly metabolically active tissue. In the current study, these 19 miRNAs were individually silenced in C2C12 myotubes using antisense oligonucleotides, followed by measurement of the expression of 27 genes known to play a major role in regulating mitochondrial metabolism. Based on the outcomes, we then focused on miR ‐382‐5p and identified pathways affected by its silencing using microarrays, investigated protein expression, and studied cellular respiration. Silencing of miRNA‐382‐5p significantly increased the expression of several genes involved in mitochondrial dynamics and biogenesis. Conventional mi croarray analysis in C2C12 myotubes silenced for miRNA‐382‐5p revealed a...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research