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Updated: Jun 12, 2026
07:55
An Improved Method to Isolate Mitochondrial Contact Sites
Published on: June 16, 2023
Mitochondria-ER contacts function as an iron supply hub.
Hijiri Oshio1, Isshin Shiiba2,3, Naoki Ito1
1Laboratory of Molecular Biochemistry, Department of Life Science, Faculty of Science, Gakushuin University, Toshima, Tokyo, Japan.
Nature Cell Biology
|June 10, 2026
Summary
This study reveals how heme provides iron to mitochondria via mitochondria-endoplasmic reticulum contact sites (MERCs). The enzyme heme oxygenase 2 (HMOX2), regulated by MITOL, ensures mitochondrial iron homeostasis and respiration.
Area of Science:
- Cellular Biology
- Mitochondrial Biology
- Metabolic Homeostasis
Background:
- Mitochondrial iron dynamics are crucial for cellular respiration and metabolic balance.
- The precise mechanisms for iron delivery into mitochondria are not fully understood.
- Mitochondria-endoplasmic reticulum contact sites (MERCs) are emerging as key regulatory hubs in cellular processes.
Purpose of the Study:
- To elucidate the molecular mechanisms of iron supply to mitochondria.
- To identify the role of heme as an iron source for mitochondria.
- To investigate the regulation of mitochondrial iron homeostasis at MERCs.
Main Methods:
- Localization studies of heme oxygenase 2 (HMOX2) at MERCs.
- Analysis of MITOL-mediated ubiquitination of HMOX2.
- Assessment of mitochondrial iron levels and respiration in knockout/mutant models.
- Investigation of mitochondrial supercomplex integrity.
Main Results:
- Heme serves as a direct iron source for mitochondria, regulated at MERCs.
- HMOX2, an ER-resident enzyme, localizes to MERCs and supplies mitochondrial iron.
- MITOL ubiquitinates HMOX2, enhancing its heme-degrading activity and iron supply.
- Disruption of HMOX2 or MITOL impairs mitochondrial iron homeostasis and respiration.
Conclusions:
- MERCs act as a critical hub for iron supply, integrating heme metabolism with mitochondrial iron utilization.
- MITOL-mediated regulation of HMOX2 at MERCs is essential for maintaining mitochondrial iron homeostasis.
- This pathway is vital for cellular respiration and overall metabolic health.
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