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Delivery Of Active Silencing RNA (siRNA) Into Mitochondria Is Possible

Gao et al., in 2020, reported that transfected siRNAs could enter the mitochondrial matrix and allow the silencing of targeted mitochondrial transcripts. The study investigated whether siRNAs and small hairpin RNAs (shRNAs) can target mitochondria DNA (mtDNA) encoded transcripts.

Small interfering RNAs (siRNAs) are powerful tools for studying gene functions and manipulating gene expression in cells. siRNAs designed following mapped argonaute 2 (Ago2)-binding peaks allowed targeting the selected mtDNA-encoded transcripts. However, since the mitoRNAi effect can be detected at the mRNA level but not on relatively unstable proteins, the research group also targeted the individual respiratory chain complex.To follow the silencing process, the research group used nuclease protection, in vitro RNA import, and click chemistry assays to detect small RNAs in the mitochondria.

Figure 1: Mitochondrial electon transport chain (Adapted from Wiki commens. METC)

Mitochondria are organelles in eukaryotic cells that function as the powerhouse of cells. Mitochondria generate adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). Mitochondria contain a genome with a modified genetic code. The human mitochondrial DNA (mtDNA) is a double-stranded, circular molecule of 16 569 bp and includes 37 genes coding for two rRNAs, 22 tRNAs, and 13 polypeptides. Mammalian mitochondrial genomes are transmitted exclusively through the female germ line.


Gao K, Cheng M, Zuo X, Lin J, Hoogewijs K, Murphy MP, Fu XD, Zhang X. Active RNA interference in mitochondria. Cell Res. 2021 Feb;31(2):219-228. [PMC]

Jan-Willem Taanman; The mitochondrial genome: structure, transcription, translation and replication. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Volume 1410, Issue 2, 1999, Pages 103-123.