In Mitochondria ?-Actin Regulates mtDNA Transcription and Is Required for Mitochondrial Quality Control.

In eukaryotic cells, actin regulates both cytoplasmic and nuclear functions. However, whether actin-based structures are present in the mitochondria and are involved in mitochondrial functions has not been investigated. Here, using wild-type ?-actin +/+ and knockout (KO) ?-actin ?/? mouse embryonic fibroblasts we show evidence for the defect in maintaining mitochondrial membrane potential (MMP) in ?-actin-null cells. MMP defects were associated with impaired mitochondrial DNA (mtDNA) transcription and nuclear oxidative phosphorylation (OXPHOS) gene expression. Using super-resolution microscopy we provided direct evidence on the presence of ?-actin-containing structures inside mitochondria. Large aggregates of TFAM-stained nucleoids were observed in bulb-shaped mitochondria in KO cells, suggesting defects in mitochondrial nucleoid segregation without ?-actin. The observation that mitochondria-targeted ?-actin rescued mtDNA transcription and MMP suggests an indispensable functional role of a mitochondrial ?-actin pool necessary for mitochondrial quality control.