Abstract
Mitochondria are vital to life and provide biological energy for other organelles and cell physiological processes. On the mitochondrial double layer membrane, there are a variety of channels and transporters to transport different metal ions, such as Ca2+, K+, Na+, Mg2+, Zn2+ and Fe2+/Fe3+. Emerging evidence in recent years has shown that the metal ion transport is essential for mitochondrial function and cellular metabolism, including oxidative phosphorylation (OXPHOS), ATP production, mitochondrial integrity, mitochondrial volume, enzyme activity, signal transduction, proliferation and apoptosis. The homeostasis of mitochondrial metal ions plays an important role in maintaining mitochondria and cell functions and regulating multiple diseases. In particular, channels and transporters for transporting mitochondrial metal ions are very critical, which can be used as potential targets to treat neurodegeneration, cardiovascular diseases, cancer, diabetes and other metabolic diseases. This review summarizes the current research on several types of mitochondrial metal ion channels/transporters and their functions in cell metabolism and diseases, providing strong evidence and therapeutic strategies for further insights into related diseases.
Highlights
Mitochondria are cytoplasmic organelles crucial to life
While some metal ion channels/transporters participate in normal physiological activities, others only play their roles in pathological states, both of which are essential for cell survival and metabolism
The influx and efflux of mitochondrial metal ions are in dynamic equilibrium
Summary
Mitochondria are cytoplasmic organelles crucial to life. Since the major function of mitochondria is to produce a large amount of energy ATP, they are called the powerhouse of the cell. It has been discovered that mitochondrial K+ transport channels including mitochondrial ATP-sensitive K+ (mitoKATP) channels, Ca2+-activated K+ (KCa) channels, voltage-gated K+ (Kv) channels, and TWIK-related acid-sensitive K+ channel 3 (mitoTASK-3) are located on the MIM [37,38,39,40,41] The functions of these K+ channels involve regulating mitochondrial respiration, maintaining membrane potential, and producing ROS [112]. Kv channels involve a variety of physiological processes ranging from triggering neuronal and cardiac action potential to regulating cell cycle and cell volume, to driving cellular proliferation and migration [16,50] These Kv channels have a major role in human diseases such as cancer, schizophrenia, epilepsy, and sudden cardiac death [50,51,53]. The transport mechanism of mitochondrial Zn2+ still needs more supporting evidence
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