A number of neurodegenerative diseases are associated with defects in the human gene AFG3L2 (MIM:604581, including spastic ataxia 5, autosomal recessive (SPAX5, FBhh0001303), spinocerebellar ataxia 28 (SCA28, FBhh0001304), and optic atrophy 12 (OPA12, FBhh0001305). AFG3L2 is the catalytic subunit of the m-AAA protease, an ATP-dependent proteolytic complex of the mitochondrial inner membrane that degrades misfolded proteins and regulates ribosome assembly. There is a single fly ortholog, Dmel\Afg3l2, for which RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated.
A UAS construct of the human Hsap\AFG3L2 gene has been introduced into flies, but has not been characterized.
Animals homozygous for amorphic alleles of Dmel\Afg3l2 die early in development. Partial knockout using RNAi allows survival to the late pupal and adult stages; these animals exhibit behavioral defects, neurodegeneration, accumulation of unfolded mitochondrial proteins, and diminished respiratory chain (RC) activity. It was determined that the reduced RC activity was primarily a consequence of severely diminished mitochondrial transcription and translation; activation of the mitochondrial unfolded protein response was observed.
[updated Jan. 2021 by FlyBase; FBrf0222196]
AFG3L2 is the catalytic subunit of the m-AAA protease, an ATP-dependent proteolytic complex of the mitochondrial inner membrane that degrades misfolded proteins and regulates ribosome assembly (summary by Koppen et al., 2007; pubmed:17101804). [from MIM:604581; 2021.01.11]
One to one: 1 human gene to 1 Drosophila gene; less closely related genes in both species.
High-scoring ortholog of human AFG3L2 (1 Drosophila to 1 human); less closely related genes in both species. Dmel\Afg3l2 shares 63% identity and 74% similarity with the human gene.
