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Updated: Jul 1, 2026
09:43
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Mitochondrial-generated G-quadruplex-forming lncRNAs regulate heme homeostasis
Vinodh J Sahayasheela1,2,3, Ryohei Noizumi1, Manendra B Lankadasari4
1Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-Ku, Kyoto 606-8502, Japan.
Iscience
|June 30, 2026
Summary
Mitochondria-generated long non-coding RNAs (mt-lncRNAs) form G-quadruplex structures that buffer heme. Disrupting these structures increases labile mitochondrial heme, impacting cellular health and disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Heme is crucial for cellular function but toxic if unregulated.
- Mitochondrial heme homeostasis depends on controlling labile heme levels.
Purpose of the Study:
- To investigate the role of mitochondria-generated long non-coding RNAs (mt-lncRNAs) in heme buffering.
- To elucidate the mechanism of heme binding by mt-lncRNAs.
Main Methods:
- G-quadruplex (G4) specific pull-down assays.
- Bio-orthogonal imaging of RNA G-quadruplex (rG4) formation.
- Cellular experiments using mitochondria-targeted inhibitors (MITO-PIP, MITO-PyPDS) and heme sensors.
- Utilized rho-zero (ρ0) cells to assess mitochondrial dependence.
Main Results:
- mt-lncRNAs contain G-quadruplex-forming sequences (rG4s) that bind heme.
- rG4 formation was observed within mt-lncRNAs in living cells.
- Disruption of mt-lncRNA rG4s led to increased labile mitochondrial heme, elevated heme in other cellular compartments, and induced oxidative stress.
- Upregulation of heme oxygenase 1 (HMOX-1) was observed.
Conclusions:
- mt-lncRNAs utilize RNA G-quadruplex structures to buffer heme within mitochondria.
- This RNA structure-based mechanism contributes to organellar metabolite homeostasis.
- Findings have implications for understanding and treating heme-related disorders and mitochondrial diseases.
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