Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme
Ke Shen1, Yixiang Zeng1, Jiekang Wang1,2
1Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bone Research
|June 29, 2026
Summary
Angiogenin (ANG) is vital for cell fusion by enabling mitochondrial ribosome biogenesis. It processes mitochondrial tRNAs, supporting energy production for cell fusion and tissue repair.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell-cell fusion is crucial for physiological processes and demands significant ATP.
- Mitochondrial activity and mitochondrial ribosome (mitoribosome) biogenesis are critical for energy supply during fusion, but the regulatory mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of angiogenin (ANG) in mitochondrial ribosome biogenesis and its impact on cell-cell fusion.
Main Methods:
- Transcriptome-wide PARE and 5' RACE analyses were employed.
- Investigated the translocation of ANG to mitochondria and its enzymatic activity on mitochondrial pre-RNA transcripts.
Main Results:
- Angiogenin (ANG) was identified as a key enzyme in mitochondrial tRNA (mt-tRNA) processing, essential for mitoribosome biogenesis.
- ANG translocates to mitochondria upon fusion initiation, cleaving mt-tRNA 3'-ends to facilitate rRNA and mRNA release for translation.
- Loss of ANG function impairs myoblast and osteoclast fusion, affecting bone and muscle homeostasis and skeletal muscle regeneration.
Conclusions:
- ANG is an essential regulator of mitoribosome biogenesis, crucial for energy production during high-demand cellular processes like cell fusion.
- This study reveals a novel mechanism for mitochondrial energy regulation mediated by ANG in cell fusion and tissue regeneration.
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