SLC25A6 is a specific protein-coding gene, also known as Solute Carrier Family 25 Member 6 or ADP/ATP translocase 3 (ANT3). This gene resides on the pseudoautosomal regions of both the X and Y chromosomes, meaning it is present on both sex chromosomes. Unusually for genes on sex chromosomes, SLC25A6 escapes X-inactivation, a process where one of the two X chromosomes in female cells is silenced. The protein produced by this gene is a fundamental component within the intricate machinery of human cells, essential for maintaining cellular life and proper function.
How SLC25A6 Powers Your Cells
Cells require a constant supply of energy for their many functions, and mitochondria serve as the primary sites for generating this energy. Often referred to as the “powerhouses” of the cell, these organelles are responsible for producing adenosine triphosphate (ATP), the main energy currency. This process, known as ATP synthesis, occurs within the mitochondrial matrix.
The protein produced by the SLC25A6 gene, ADP/ATP translocase 3 (ANT3), plays a central role in this energy production by acting as an ADP:ATP antiporter. ANT3 imports adenosine diphosphate (ADP) into the mitochondrial matrix, where it can be converted into ATP.
Once ATP is synthesized within the matrix, ANT3 then exports this ATP out of the mitochondrion and into the cytoplasm. This continuous exchange ensures that the cell has ATP to power its various energy-dependent processes. The protein operates through an alternating access mechanism to expose a single substrate-binding site to either the cytoplasm or the mitochondrial matrix.
ANT3 cycles between cytoplasmic-open and matrix-open states. In the cytoplasmic-open state, it binds ADP from the cytoplasm and moves it into the matrix. Conversely, in the matrix-open state, it binds ATP from the matrix and releases it into the cytoplasm. This precise and regulated movement of ADP and ATP is a core function, directly linking mitochondrial energy production to the energy demands of the entire cell.
SLC25A6’s Other Vital Functions
Beyond its primary role in ATP/ADP exchange, SLC25A6 also participates in other significant mitochondrial processes. It involves mitochondrial uncoupling, a process that can separate the production of heat from ATP synthesis. SLC25A6 can act as a proton transporter, allowing protons to bypass the normal ATP synthesis pathway and instead generate heat.
This proton transport activity contributes to mitochondrial thermogenesis. This mechanism is relevant in regulating body temperature. The ability of SLC25A6 to switch between facilitating ATP/ADP exchange and transporting protons suggests a complex regulatory role within the cell’s energy management.
The proton transporter activity of SLC25A6 is inhibited when its ADP:ATP antiporter activity is high. This suggests a balance where the cell prioritizes ATP production when energy is needed, but can shift towards heat generation. This dual function positions SLC25A6 as a regulator of overall mitochondrial energy output, balancing ATP supply and heat production.
SLC25A6 plays a significant role in the opening of the mitochondrial permeability transition pore (mPTP). The mPTP is a channel that forms in the inner mitochondrial membrane under certain stress conditions. Its opening leads to an increase in the permeability of the inner mitochondrial membrane, causing the mitochondrion to swell and lose its membrane potential. This disruption releases various pro-apoptotic factors from the mitochondrion into the cytoplasm. The sustained opening of the mPTP can trigger apoptosis, a form of programmed cell death.
When SLC25A6 Goes Wrong: Disease Connections
Dysfunction of the SLC25A6 protein has been linked to several disease states and cellular pathways. The protein is associated with serious bacterial infections such as Plague. Disruptions in mitochondrial function, which SLC25A6 directly influences, can contribute to the severe cellular damage in these diseases.
SLC25A6 is also implicated in pathways relevant to neurodegenerative conditions, including Alzheimer’s disease. Disruptions in mitochondrial energy metabolism and increased cellular stress are hallmarks of the disease. Its central role in mitochondrial function and cell death pathways suggests its malfunction could contribute to neuronal dysfunction and loss in such conditions.
The protein also interacts with various other proteins, including those derived from viruses. For example, the influenza A virus produces a protein called PB1-F2, which has been shown to interact with mitochondrial proteins like ANT3. This interaction can contribute to the cell death induced by the influenza virus, potentially by affecting mitochondrial integrity and function.
Similarly, the HIV-1 Vpr protein also interacts with mitochondrial components, including ANT3. These viral proteins exploit SLC25A6 to induce cell death in infected cells. By manipulating this protein, viruses can subvert cellular processes to their advantage, leading to the demise of the host cell.