Transmembrane protein 126A (TMEM126A)

Transmembrane protein 126A (TMEM126A) is a conserved mitochondrial inner membrane protein, highly enriched in the mitochondrial cristae[1][5]. It is primarily known as an assembly factor required for the proper formation and function of mitochondrial complex I (the first complex in the mitochondrial respiratory chain)[1]. TMEM126A specifically interacts with the newly synthesized ND4 subunit of mitochondrial complex I and participates in the assembly of the ND4 distal membrane module[1]. Loss of TMEM126A leads to isolated complex I deficiency, causing reduced cellular ATP production and resulting in diseases especially affecting tissues with high-energy demands, such as retinal ganglion cells[1][5]. Mutations in TMEM126A are the cause of autosomal recessive optic atrophy type 7 (OPA7); patients typically present with early-onset bilateral visual acuity loss, optic nerve pallor, and central scotoma[2][4]. Some patients additionally show mild hypertrophic cardiomyopathy and hearing loss[1]. TMEM126A is expressed in various tissues including parathyroid gland, prostate, uterus, kidney, heart, brain and peripheral blood cells[3]. TMEM126A has known paralog TMEM126B, which is also an assembly factor but not functionally redundant[1][3]. No drugs are currently known to directly target TMEM126A and it is not considered a classical therapeutic target such as a receptor, enzyme, ion channel, or transporter[1][3][5]. However, genetic testing for TMEM126A mutations is a biomarker for certain forms of optic atrophy[2][4].

Other names

Optic atrophy 7OPA7DKFZp586C1924