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Updated: Jun 5, 2026

Dual-color Correlative Light and Electron Microscopy for the Visualization of Interactions between Mitochondria and Lysosomes
Published on: September 27, 2024
Possible existence of lysosome-like organella within mitochondria and its role in mitochondrial quality control
Yuji Miyamoto1, Noriaki Kitamura, Yasuyuki Nakamura
1Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
The accumulation of unhealthy mitochondria results in mitochondrial dysfunction, which has been implicated in aging, cancer, and a variety of degenerative diseases. However, the mechanism by which mitochondrial quality is regulated remains unclear. Here, we show that Mieap, a novel p53-inducible protein, induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control. Mieap expression is directly regulated by p53 and is frequently lost in human cancer as result of DNA methylation. Mieap dramatically induces the accumulation of lysosomal proteins within mitochondria and mitochondrial acidic condition without destroying the mitochondrial structure (designated MALM, for Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage. MALM was not related to canonical autophagy. MALM is involved in the degradation of oxidized mitochondrial proteins, leading to increased ATP synthesis and decreased reactive oxygen species generation. These results suggest that Mieap induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control by eliminating oxidized mitochondrial proteins. Cancer cells might accumulate unhealthy mitochondria due to p53 mutations and/or Mieap methylation, representing a potential cause of the Warburg effect.
Insights
Mieap protein triggers intramitochondrial lysosome-like organelles (MALM) for mitochondrial quality control. This process degrades damaged proteins, enhancing ATP synthesis and reducing oxidative stress, offering insights into cancer development.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Molecular Oncology
Background:
- Mitochondrial dysfunction is linked to aging, cancer, and degenerative diseases.
- Mechanisms regulating mitochondrial quality control are not fully understood.
- Mitochondrial health is crucial for cellular function and disease prevention.
Purpose of the Study:
- To investigate the role of Mieap in mitochondrial quality control.
- To elucidate the mechanism of Mieap-induced mitochondrial regulation.
- To explore the implications of Mieap in cancer and aging.
Main Methods:
- Analysis of Mieap expression and regulation by p53.
- Induction of Mieap-induced accumulation of lysosome-like organelles within mitochondria (MALM).
- Assessment of mitochondrial protein degradation, ATP synthesis, and reactive oxygen species (ROS) generation.
Main Results:
- Mieap, a p53-inducible protein, forms intramitochondrial lysosome-like organelles (MALM).
- MALM facilitates the degradation of oxidized mitochondrial proteins, independent of canonical autophagy.
- Mieap expression is lost in human cancers due to DNA methylation, potentially contributing to the Warburg effect.
Conclusions:
- Mieap-induced MALM is a novel mechanism for mitochondrial quality control.
- This pathway degrades damaged mitochondrial proteins, improving mitochondrial function.
- Dysregulation of Mieap in cancer may lead to accumulation of unhealthy mitochondria and altered metabolism.
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