ATP-dependent metalloprotease YME1L1 is an enzyme that in humans is encoded by the YME1L1gene.[1] YME1L1 belongs to the AAA family of ATPases and mainly functions in the maintenance of mitochondrial morphology. Mutations in this gene would cause infantile-onset mitochondriopathy.[2]
The YME1L1 gene is located at chromosome 10p14, consisting of 20 exons. Two transcript variants encoding different isoforms have been found for this gene.
YME1L1 is embedded in the inner mitochondrial membrane and is more abundant in tissues with a high content of mitochondria such as human adult heart, skeletal muscle, and pancreasRNA.[3][2] YME1L1 is a member of the AAA family of ATPases and has an important role for the maintenance of mitochondrial morphology.[2] Its mature form assembles into a homo-oligomeric complex within the inner mitochondrial membrane (IM).[4] It degrades both intermembrane space and IM proteins, including lipid transfer proteins, components of protein translocases of the IM, and the dynamin-like GTPase optic atrophy 1 (OPA1) [5][6][7] Loss of YME1L1 accelerates OMA1-dependent long-form OPA1 cleavage, resulting in short-form OPA1 accumulation, increased mitochondrial fission, and mitochondrial network fragmentation.[8] It’s also reported that YME1L1 controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation.[9]
Clinical significance
A homozygous mutation in the YME1L1 gene would cause infantile-onset mitochondriopathy, with severe intellectual disability, muscular impairments, and optic nerve atrophy. The missense mutation affects the MPP processing site and impairs YME1L1 maturation, leading to its rapid degradation, and also leads to a proliferation defect, abnormal OPA1 processing and mitochondrial fragmentation.[2]
↑ 3.03.1Coppola M, Pizzigoni A, Banfi S, Bassi MT, Casari G, Incerti B (May 2000). "Identification and characterization of YME1L1, a novel paraplegin-related gene". Genomics. 66 (1): 48–54. doi:10.1006/geno.2000.6136. PMID10843804.
↑Van Dyck L, Langer T (November 1999). "ATP-dependent proteases controlling mitochondrial function in the yeast Saccharomyces cerevisiae". Cellular and Molecular Life Sciences. 56 (9–10): 825–42. doi:10.1007/s000180050029. PMID11212342.
↑Potting C, Tatsuta T, König T, Haag M, Wai T, Aaltonen MJ, Langer T (August 2013). "TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid". Cell Metabolism. 18 (2): 287–95. doi:10.1016/j.cmet.2013.07.008. PMID23931759.
↑MacVicar T, Langer T (June 2016). "OPA1 processing in cell death and disease - the long and short of it". Journal of Cell Science. 129 (12): 2297–306. doi:10.1242/jcs.159186. PMID27189080.
Further reading
Shah ZH, Hakkaart GA, Arku B, de Jong L, van der Spek H, Grivell LA, Jacobs HT (August 2000). "The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p complements a yeast yme1 disruptant". FEBS Letters. 478 (3): 267–70. doi:10.1016/S0014-5793(00)01859-7. PMID10930580.
Pellegrini L, Passer BJ, Canelles M, Lefterov I, Ganjei JK, Fowlkes BJ, Koonin EV, D'Adamio L (April 2001). "PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2". Journal of Alzheimer's Disease. 3 (2): 181–190. PMID12214059.
