Related Experiment Video
Updated: Jul 13, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Regulation of transient receptor potential melastatin 7 (TRPM7) currents by mitochondria
Byung Joo Kim1, Ju-Hong Jeon, Seon Jeong Kim
1Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Abstract:
Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of F1/FO-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial Ca2+ uniporter, and ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the F1/FO-ATP synthase of mitochondria are important in regulating TRPM7 channels.
Insights
Mitochondria regulate the TRPM7 ion channel. Changes in mitochondrial membrane potential and ATP synthase activity, influenced by proton ionophores and oligomycin, affect TRPM7 channel function.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Physiology
Background:
- Mitochondria are crucial for cellular energy production.
- Mitochondria are increasingly recognized for their roles in regulating ion channels and receptors.
- The transient receptor potential melastatin 7 (TRPM7) is a bifunctional enzyme with both ion channel and kinase activity.
Purpose of the Study:
- To investigate the role of mitochondria in regulating the TRPM7 ion channel.
- To elucidate how mitochondrial function impacts TRPM7 channel activity.
Main Methods:
- Whole-cell patch-clamp electrophysiology was used to record TRPM7 currents.
- Mitochondrial function was manipulated using proton ionophores (CCCP) and inhibitors of ATP synthase (oligomycin).
- Specific inhibitors of respiratory chain complexes (rotenone, antimycin A) and mitochondrial calcium uniporter (kaempferol, ruthenium red) were employed.
Main Results:
- Proton ionophores (CCCP) altered TRPM7 currents in a MgATP-dependent manner, decreasing outward currents and increasing inward currents without MgATP, but increasing both with MgATP.
- Oligomycin inhibited outward TRPM7 currents, suggesting a role for ATP synthase.
- Inhibitors of respiratory chain complexes I and III, and mitochondrial calcium uniporter modulators, did not significantly affect TRPM7 currents.
Conclusions:
- Mitochondrial inner membrane potential, modulated by proton ionophores, is a key regulator of TRPM7 channel activity.
- The F1/FO-ATP synthase is involved in regulating outward TRPM7 currents.
- Mitochondria represent a significant regulatory influence on TRPM7 channel function.
Related Concept Videos
Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Protein Transport into the Inner Mitochondrial Membrane
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Mitochondrial Precursor Proteins
Most of the mitochondrial precursors...
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Mechanically-gated Ion Channels

