TOMM22 is an integral mitochondrial outer membrane protein with three functional domains:
N-terminal cytosolic domain: Binds mitochondrial preproteins in cooperation with TOM20 .
Transmembrane domain: Anchors the protein and maintains TOM complex integrity .
C-terminal intermembrane space domain: Facilitates precursor protein translocation .
TOMM22 serves as a central receptor in the TOM complex, enabling the import of nuclear-encoded mitochondrial proteins . Dysregulation of TOMM22 is linked to mitochondrial dysfunction, cardiomyopathies, and neurodegenerative diseases .
TOMM22 interacts with pro-apoptotic protein Bax, facilitating its mitochondrial localization during apoptosis .
Antibodies against TOMM22 (e.g., ab57523) block Bax-dependent apoptosis in vitro .
TOMM22 mediates mitochondrial surface binding of Aβ peptides, contributing to Alzheimer’s disease pathology .
Conformational antibodies (e.g., Fab fragments) targeting TOMM22 reduce Aβ accumulation in yeast models .
Phosphorylation sites: S15 and T43 in mice are phosphorylated by CSNK2/CK2, regulating mitophagy .
Functional impact: Phosphomimetic TOMM22 mutants restore mitochondrial respiration in Csnk2b-deficient cells .
| Antibody | Observed Band | Lysate/Cell Line |
|---|---|---|
| ab246862 | 15 kDa | U-2 OS (siRNA-treated) |
| 11278-1-AP | 15–22 kDa | HeLa, Mouse liver |
| 90704 (Cell Signaling) | 20 kDa | Human cell lines |
Neurodegeneration: Impaired TOMM22 function correlates with mitochondrial Aβ accumulation .
Muscle disorders: Csnk2b knockout mice show muscle weakness and abnormal mitophagy due to TOMM22 dysregulation .
Cardiomyopathy: TOMM22 deficiency disrupts mitochondrial calcium import, leading to cardiomyocyte dysfunction .