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

Summary

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

Graphical Abstract

Highlights

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  Maintenance of mitochondrial membrane potential (MMP) requires β-actin

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  MMP defects are due to impaired mtDNA and nucleus-encoded OXPHOS gene transcription

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  Loss of mitochondrial β-actin-containing structures leads to nucleoid aggregation

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  Mitochondria-targeted β-actin rescued mtDNA transcription and MMP

Abstract

Molecular Biology; Cell Biology; Functional Aspects of Cell Biology