YME1L1: A Key Regulator of Mitochondrial Proteostasis and Dynamics
Comprehensive genomic and functional analysis of the YME1L1 gene, encoding an ATP-dependent metalloprotease essential for mitochondrial inner membrane integrity, cristae biogenesis, and cellular stress responses.
Gene Information Card
| Symbol | YME1L1 |
|---|---|
| Full Name | YME1 like 1 ATPase |
| Gene Type | Protein coding |
| Chromosomal Location | 10p12.1 |
| NCBI Gene ID | 10730 ncbi.nlm.nih.gov/gene/10730 |
| Ensembl ID | ENSG00000136732 |
| UniProt ID | Q96TA2 |
| OMIM ID | 607472 |
| HGNC ID | 12844 |
| Aliases | YME1L, FTSH, MEG4, OPA11, PAMP, YME1L1 variant 1 |
Description
YME1L1 encodes an ATP-dependent zinc metalloprotease of the AAA+ family, localized to the mitochondrial inner membrane. It is essential for maintaining mitochondrial proteostasis by degrading misfolded or damaged proteins, processing the dynamin-like GTPase OPA1 to regulate cristae morphology, and coordinating mitochondrial dynamics. Loss-of-function mutations cause autosomal dominant optic atrophy type 11 (OPA11) and are implicated in neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Optic atrophy 11 (OPA11) | Loss-of-function mutations impair OPA1 processing, leading to mitochondrial fragmentation and retinal ganglion cell degeneration. | OMIM #618083; ClinVar pathogenic variants |
| Neurodegeneration with ataxia and optic atrophy | Biallelic YME1L1 variants disrupt mitochondrial proteostasis, causing progressive neurological decline. | PMID: 31585109; ClinVar |
| Mitochondrial encephalopathy | Defective YME1L1 activity results in accumulation of toxic mitochondrial proteins and energy failure. | PMID: 31585109; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | High |
| Skeletal muscle | 10.8 | High |
| Brain | 8.2 | Medium |
| Liver | 6.1 | Medium |
| Kidney | 7.4 | Medium |
| Pancreas | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.3 | High expression; used in functional studies |
| HEK293 | 8.7 | High expression; common model |
| SH-SY5Y | 7.1 | Medium expression; neuronal model |
| HepG2 | 6.5 | Medium expression |
| K562 | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1186C>T (p.Arg396Trp) | Missense | Rare | Loss of ATPase activity; dominant optic atrophy |
| c.1492G>A (p.Gly498Arg) | Missense | Rare | Impaired substrate processing; neurodegeneration |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of function; severe phenotype |
| c.2050_2051del (p.Lys684Glufs*3) | Frameshift | Rare | Truncated protein; loss of proteolytic activity |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic YME1L1 mutations are loss-of-function, reducing ATPase or proteolytic activity, leading to defective OPA1 processing and mitochondrial fragmentation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for YME1L1.
Dominant Negative (DN)
Dominant-negative effects are hypothesized for some missense variants (e.g., p.Arg396Trp) that interfere with the hexameric complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • ATP-dependent peptidase activity | • metallopeptidase activity |
| • mitochondrial inner membrane | • protein quality control |
| • mitochondrial cristae biogenesis | • mitochondrial fusion |
| • response to stress | • proteolysis |
Pathways
• Mitochondrial protein degradation (Reactome R-HSA-8949215)
• OPA1 processing and mitochondrial dynamics (Reactome R-HSA-8949216)
• Mitochondrial unfolded protein response (UPRmt)
Protein Summary
YME1L1 is a 716-amino acid ATP-dependent zinc metalloprotease anchored in the mitochondrial inner membrane. It forms a hexameric complex that degrades misfolded proteins and processes OPA1 to maintain cristae structure. The protein contains an AAA+ ATPase domain and a zinc-binding motif essential for proteolysis. Dysfunction leads to mitochondrial fragmentation, impaired oxidative phosphorylation, and cell death, particularly in high-energy-demand tissues like neurons and muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| YME1L1 Knockout HEK293 Cell Line | EDJ-KQ971 | Human | 10730 | Details Get a Quote |
| YME1L1 Knockout HCT 116 Cell Line | EDJ-KQ19981 | Human | 10730 | Details Get a Quote |
| YME1L1 Knockout HeLa Cell Line | EDJ-KQ19982 | Human | 10730 | Details Get a Quote |
| YME1L1 Knockout A-549 Cell Line | EDJ-KQ63959 | Human | 10730 | Details Get a Quote |
