ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs.
Cell Res
; 34(7): 504-521, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38811766
ABSTRACT
Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Double-Stranded
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Adenine Nucleotide Translocator 2
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Mitochondrial Membranes
/
Mitochondria
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Res
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: