ATAD3A
Domain
The transmembrane domain and a C-terminal adjacent region contain all information necessary for mitochondrial targeting.
Function
Essential for mitochondrial network organization, mitochondrial metabolism and cell growth at organism and cellular level (PubMed:17210950, PubMed:20154147, PubMed:22453275, PubMed:31522117, PubMed:37832546, PubMed:39116259). May play an important role in mitochondrial protein synthesis (PubMed:22453275). May also participate in mitochondrial DNA replication (PubMed:17210950). May bind to mitochondrial DNA D-loops and contribute to nucleoid stability (PubMed:17210950). Required for enhanced channeling of cholesterol for hormone-dependent steroidogenesis (PubMed:22453275). Involved in mitochondrial-mediated antiviral innate immunity (PubMed:31522117). Required to protect mitochondria from the PERK-mediated unfolded protein response: specifically inhibits the activity of EIF2AK3/PERK at mitochondria-endoplasmic reticulum contact sites, thereby providing a safe haven for mitochondrial protein translation during endoplasmic reticulum stress (PubMed:39116259). Ability to inhibit EIF2AK3/PERK is independent of its ATPase activity (PubMed:39116259). Also involved in the mitochondrial DNA damage response by promoting signaling between damaged genomes and the mitochondrial membrane, leading to activation of the integrated stress response (ISR) (PubMed:37832546).
Involvement in disease
Harel-Yoon syndrome
HAYOS
A syndrome characterized by global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. Some patients have optic atrophy and hypertrophic cardiomyopathy. HAYOS inheritance can be autosomal dominant or autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal
PHRINL
An autosomal recessive multisystem disorder with onset in utero and death in the neonatal period. Affected infants show respiratory insufficiency and almost no spontaneous movement at birth. Additional features include corneal clouding, seizures, dysmorphic facies, contractures, and progressive pontocerebellar hypoplasia with simplified gyral pattern and white matter abnormalities. Some patients may have cardiac anomalies or cardiac hypertrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the AAA ATPase family.
Tissue Specificity
Overexpressed in lung adenocarcinomas (at protein level).
Cellular localization
- Mitochondrion inner membrane
- Single-pass membrane protein
- Mitochondrion matrix
- Mitochondrion nucleoid
- In the mitochondrial inner membrane, enriched in sites with the potential to form contacts with the outer membrane (PubMed:20154147, PubMed:20349121). The N-terminal domain interacts with the inner surface of the mitochondrial outer membrane and the C-terminal domain localizes in a specific matrix compartment, where it is associated with nucleoids (PubMed:18063578). Also present at mitochondria-endoplasmic reticulum contact sites; where it interacts with EIF2AK3/PERK (PubMed:39116259).
Alternative names
ATPase family AAA domain-containing protein 3A, ATAD3A