About SDHAF / Succinate Dehydrogenase Complex Assembly Factor:
Succinate dehydrogenase complex assembly factor 1 (SDHAF1) is a chaperone protein used in the assembly of the succinate dehydrogenase (SDH) complex (complex II). It is also known as LYR motif-containing protein 8 (LYRM8).
Mutations in SDHAF1 are strongly linked with mitochondrial complex II deficiency. Although this is a disorder of the mitochondrial respiratory chain it has a wide range of psychomotor manifestations. SDHAF1 mutations are also strongly linked with SDH-defective infantile leukoencephalopathy.
The SDHAF1 protein shields SDHB from the oxidants which could otherwise damage it. This enables the assembly and stabilization of the succinate dehydrogenase (SDH) complex (complex II). SDH is necessary for both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain.
It also binds directly to the co-chaperone protein HSC20. This enables the scaffold protein ISCU to transfer the Fe-S prosthetic group to recipient apoproteins (namely SDHB). Indirectly, therefore, the SDHAF1 protein makes it possible for SDHB to acquire Fe-S clusters.
Succinate Dehydrogenase Complex Assembly Factor Structure
The SDHAF1 gene is located in position 13.12 of the q arm of chromosome 19 (19q13.12). It has 1 exon. The SDHAF1 protein is a 12.8 kDa protein. It consists of 115 amino acids.
SDHAF1 has a total of 27 protein-protein interactions. Of these, 15 are co-complex interactions. Genes known to interact with SDHAF1 include:
Succinate Dehydrogenase Complex Assembly Factor Mechanism of action
An arginine-rich region in the C terminus of SDHAF1 creates a transient bond with the aromatic peptides of SDHB. This engages specifically with an Fe-S donor complex through an LYR motif near its N-terminal domain. The scaffold is holo-ISCU, and the co-chaperone-chaperone pair is HSC20-HSPA9.