Ion channel-mediated mitochondrial volume regulation and its relationship with mitochondrial dynamics

Figures & data

Table 1. Mitochondrial ion channels described in this article.

	Type	Role(s)	Selected refs.
1	KATP	Volume regulation, protection against apoptosis/ischemic injury	[16,22]
2	K+ leak	Volume regulation	[14]
3	K+/H+ antiporter	Volume regulation	[26,27]
4	Ca^2+ uniporter	Ca^2+ uptake	[31]
5	KCa	Volume regulation	[32–34]
6	VDAC	Metabolite transport, Cytochrome c release/apoptosis, PTP complex	[38]
7	IMACs	Volume regulation	[34,40]
8	ClIC4,5	Volume regulation,apoptosis	[43]

Figure 1. Overview of mitochondrial K⁺ transport.

A line diagram shows the electron transport chain, electrochemical gradient and locations of potassium leak channels and ATP-sensitive potassium channel (MitoKATP) on the inner mitochondrial membrane. It also labels the subunits of MitoKATP. Arrows indicate the direction of potassium transport.

Because of proton pumping by the electron transport chain (ETC) coupled with the reduction of oxygen and oxidation of coenzymes, the mitochondrion has an electrochemical gradient, with a negatively charged matrix. K⁺ leak across the inner membrane is quantitatively relevant owing to the high concentrations of this ion in the cytosol and the electrochemical gradient. K⁺ ions also enter the matrix through the ATP-sensitive K⁺ channel (KATP or MitoKATP). The channel is formed by two subunits: MitoKIR (or MitoK) and MitoSUR. K⁺ is removed from the mitochondrial matrix in exchange for H⁺

Figure 2. Cation fluxes that regulate mitochondrial matrix volume.

A schematic diagram labels the ion channels and transporters involved in regulating mitochondrial matrix volume, including potassium channels, sodium-hydrogen exchanger, sodium-calcium exchanger and aquaporin.

K_Ca, Ca²⁺-dependent K⁺ channel, KATP, ATP-dependent K⁺ channel, KHE, K⁺/H⁺ exchanger, NHE, Na⁺/H⁺ exchanger, Na/Ca, Na⁺/Ca²⁺ exchanger, AQP, aquaporin; PTP, permeability transition pore.

Figure 3. Regulation of chloride intracellular channels (CLICs).

Text that states chloride intracellular channels (CLICs) are involved in various cellular functions including membrane transport, cell skeleton function, cell cycle regulation, tubular system generation, vascular endothelial cell generation, mitosis and differentiation.

CLICs are involved in membrane transport, cell skeleton function, cell cycle regulation, tubular system generation, vascular endothelial cell generation, mitosis and differentiation.

Figure 4. Mechanism of mitochondrial dynamics.

Text that describes mitochondrial dynamics as a balance of fission and fusion, and how cellular stress can disrupt this balance, leading to changes in mitochondrial and cellular homeostasis, and even apoptosis. It also outlines the roles of mitochondrial networks and fragmentation under mild versus severe stress.

The mitochondrion is in a dynamic equilibrium of simultaneous fission and fusion, and this equilibrium is disrupted when the internal and external cellular environments change. When cells experience mild stress, the mitochondrion forms an elongated and interconnected network to resist mitochondrial autophagy and to increase ATP production, thereby adapting to stressful conditions such as cellular undernutrition. By contrast, under severe stress, the mitochondrion becomes fragmented. When the dynamics of mitochondrial fission and fusion become unbalanced, intracellular homeostasis is disturbed, leading to mitochondrial autophagy and even apoptosis.

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.