In Mitochondria β-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 beta-actin +/+ and knockout (KO) b-actin -/- mouse embryonic fibroblasts we show evidence for the defect in maintaining mitochondrial membrane potential (MMP) in beta-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 beta-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 beta-actin. The observation that mitochondria-targeted beta-actin rescued mtDNA transcription and MMP suggests an indispensable functional role of a mitochondrial beta-actin pool necessary for mitochondrial quality control.