YME1L1
Description
The YME1L1 (YME1 like 1 ATPase) is a protein-coding gene located on chromosome 10.
YME1L1 is a human gene that encodes an ATP-dependent metalloprotease responsible for maintaining mitochondrial morphology. Mutations in this gene lead to infantile-onset mitochondriopathy. The YME1L1 gene is located on chromosome 10p14 and contains 20 exons. Two transcript variants encoding different isoforms have been identified. The YME1L1 protein contains 716 amino acids and shares significant similarity with other mitochondrial AAA proteases, particularly yeast Yme1p. It contains three key domains: an AAA consensus sequence, an ATP/GTP binding motif, and a HEXXH motif characteristic of zinc-dependent binding domains. YME1L1 is embedded in the inner mitochondrial membrane and is abundant in tissues with high mitochondrial content, such as the heart, skeletal muscle, and pancreas. It forms a homo-oligomeric complex within the inner mitochondrial membrane and degrades both intermembrane space and inner membrane proteins, including lipid transfer proteins, components of protein translocases, and the dynamin-like GTPase OPA1. Loss of YME1L1 accelerates OMA1-dependent cleavage of long-form OPA1, leading to accumulation of short-form OPA1, increased mitochondrial fission, and fragmentation of the mitochondrial network.
YME1L1 is a mitochondrial metalloprotease that degrades both folded and unfolded proteins within the mitochondrial intermembrane space. It plays a critical role in regulating mitochondrial morphology and function. YME1L1 cleaves OPA1 at position S2, generating a form of OPA1 that promotes normal mitochondrial structure and protein metabolism. It also contributes to cell proliferation, maintaining normal cristae morphology and complex I respiration activity. Additionally, YME1L1 protects mitochondria from accumulating oxidatively damaged membrane proteins, ensuring proper mitochondrial function. YME1L1 is essential for the degradation of PRELID1 and OMA1 in response to membrane depolarization. It also controls the accumulation of nonassembled respiratory chain subunits, ensuring proper assembly and function of the electron transport chain.
YME1L1 is also known as FTSH, MEG4, OPA11, PAMP, YME1L.
