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Updated: Apr 30, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
The mitochondrial permeability transition pore is a dispensable element for mitochondrial calcium efflux
Elena De Marchi1, Massimo Bonora1, Carlotta Giorgi1
1Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Abstract:
The mitochondrial permeability transition pore (mPTP) has long been known to have a role in mitochondrial calcium (Ca(2+)) homeostasis under pathological conditions as a mediator of the mitochondrial permeability transition and the activation of the consequent cell death mechanism. However, its role in the context of mitochondrial Ca(2+) homeostasis is not yet clear. Several studies that were based on PPIF inhibition or knock out suggested that mPTP is involved in the Ca(2+) efflux mechanism, while other observations have revealed the opposite result. The c subunit of the mitochondrial F1/FO ATP synthase has been recently found to be a fundamental component of the mPTP. In this work, we focused on the contribution of the mPTP in the Ca(2+) efflux mechanism by modulating the expression of the c subunit. We observed that forcing mPTP opening or closing did not impair mitochondrial Ca(2+) efflux. Therefore, our results strongly suggest that the mPTP does not participate in mitochondrial Ca(2+) homeostasis in a physiological context in HeLa cells.
Insights
The mitochondrial permeability transition pore (mPTP) does not affect calcium efflux in HeLa cells. This study suggests mPTP is not involved in physiological mitochondrial calcium homeostasis.
Area of Science:
- Cell Biology
- Biochemistry
- Mitochondrial Physiology
Background:
- The mitochondrial permeability transition pore (mPTP) is implicated in calcium homeostasis and cell death.
- Its precise role in physiological calcium handling remains debated.
- The c subunit of ATP synthase is a key component of the mPTP.
Purpose of the Study:
- To investigate the role of the mPTP in mitochondrial calcium (Ca2+) efflux.
- To determine if modulating the mPTP affects Ca2+ homeostasis.
- To clarify the mPTP's function in physiological calcium handling.
Main Methods:
- Modulating the expression of the c subunit of the mitochondrial F1/FO ATP synthase.
- Forcing the opening or closing of the mPTP.
- Measuring mitochondrial Ca2+ efflux in HeLa cells.
Main Results:
- Forcing mPTP opening or closing did not alter mitochondrial Ca2+ efflux.
- The study found no impairment in Ca2+ efflux under manipulated mPTP conditions.
- Results indicate a lack of mPTP involvement in Ca2+ efflux.
Conclusions:
- The mPTP does not appear to play a significant role in mitochondrial calcium efflux.
- The mPTP is likely not involved in physiological mitochondrial calcium homeostasis in HeLa cells.
- Further research may be needed to fully elucidate the mPTP's function.
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