Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression

Area of Science:

• Cell Biology
• Molecular Biology
• Mitochondrial Biology

Background:

• Mitochondrial gene expression is compartmentalized, with DNA replication/transcription at nucleoids and RNA processing/ribosome assembly at RNA granules.
• Bidirectional mitochondrial DNA (mtDNA) transcription can produce immunogenic mitochondrial double-stranded RNA (mt-dsRNA).
• Mechanisms regulating mt-dsRNA localization and homeostasis remain largely uncharacterized.

Purpose of the Study:

• To investigate the localization and regulation of mitochondrial double-stranded RNA (mt-dsRNA).
• To understand the relationship between cell proliferation and mt-dsRNA homeostasis.
• To identify factors influencing mt-dsRNA abundance.

Main Methods:

• Super-resolution microscopy was employed to visualize mt-dsRNA localization within mitochondria.
• Cell proliferation was stimulated to observe changes in mt-dsRNA foci.
• The role of nucleoside diphosphate kinase NME6 in mt-dsRNA homeostasis was assessed.

Main Results:

• Mitochondrial double-stranded RNA (mt-dsRNA) was found to overlap with mitochondrial RNA granules, not nucleoids.
• mt-dsRNA foci accumulation correlated with stimulated cell proliferation.
• The abundance of mt-dsRNA foci was dependent on mitochondrial ribonucleotide supply mediated by NME6.

Conclusions:

• Mitochondrial double-stranded RNA (mt-dsRNA) localizes to mitochondrial RNA granules.
• Cell proliferation stimulates the accumulation of mt-dsRNA, influenced by NME6-dependent nucleotide supply.
• A novel link between cell proliferation and mitochondrial nucleic acid homeostasis involving mt-dsRNA is established.