Mitochondrial proton/calcium exchanger protein
Function
Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:18628306, PubMed:19797662, PubMed:24344246, PubMed:24898248, PubMed:29123128, PubMed:32139798, PubMed:36055214, PubMed:36321428). Mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662, PubMed:24344246, PubMed:29123128). Functions also as an electroneutral mitochondrial proton/potassium exchanger (PubMed:24898248, PubMed:36055214, PubMed:36321428). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (PubMed:18628306, PubMed:36055214). Required for the maintenance of the tubular shape and cristae organization (PubMed:18628306, PubMed:32139798).
Involvement in disease
Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
CONDMIM
An autosomal recessive disorder characterized primarily by global developmental delay and variably impaired intellectual development with speech delay apparent from infancy. Affected individuals have hypotonia, poor feeding, poor overall growth, and respiratory distress early in life. Other features include visual impairment due to optic atrophy, sensorineural hearing loss, and neuromuscular abnormalities. Features suggestive of a mitochondrial disorder include cataracts, cardiomyopathy, diabetes mellitus, combined oxidative phosphorylation deficiency, and increased lactate. Some patients develop seizures, some have dysmorphic facial features, and some have non-specific abnormalities on brain imaging. Death in childhood may occur.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
PINK1-mediated phosphorylation at Thr-192, positively regulates its mitochondrial calcium transport activity.
Sequence Similarities
Belongs to the LETM1 family.
Cellular localization
- Mitochondrion inner membrane
- Single-pass membrane protein
Alternative names
Mitochondrial proton/calcium exchanger protein, Electroneutral mitochondrial K(+)/H(+)exchanger, Leucine zipper-EF-hand-containing transmembrane protein 1, KHE, LETM1