The TIMM44 antibody targets the translocase of inner mitochondrial membrane 44 (TIMM44), a protein critical for mitochondrial integrity and function. TIMM44 anchors mitochondrial heat shock protein 70 (mtHsp70) to the TIMM23 complex in an ATP-dependent manner, facilitating protein import into the mitochondrial matrix . Dysregulation of TIMM44 disrupts mitochondrial functions, leading to ATP depletion, oxidative stress, and apoptosis .
Immunogen: Recombinant TIMM44 fusion protein (Ag4834 or Ag21389) .
Observed Molecular Weight: 45 kDa (mature form) , differing from the predicted 51 kDa due to post-translational modifications .
TIMM44 antibodies have been used to study its role in mitochondrial pre-protein translocation. TIMM44 anchors mtHsp70 to the TIMM23 complex, enabling ATP-dependent import of proteins with folded domains . Mutational studies in yeast (tim44-804) show that TIMM44 is critical for recruiting motor subunits like Pam17 and the J-complex to the TIM23 translocase .
Inhibition of Angiogenesis: TIMM44 silencing in endothelial cells (via shRNA or CRISPR-Cas9) suppresses proliferation, migration, and capillary tube formation by disrupting mitochondrial protein import, reducing ATP, and increasing ROS .
Retinal Angiogenesis: Endothelial-specific TIMM44 knockdown in mice reduces retinal vascular branches, increases vascular leakage, and causes retinal ganglion cell degeneration .
Therapeutic Target: The TIMM44 inhibitor MB-10 ("MitoBloCK-10") mimics silencing effects, suggesting potential for treating diseases with abnormal angiogenesis .
Parameter | TIMM44 Silencing/KO | TIMM44 Overexpression |
---|---|---|
ATP Production | ↓ 70–80% | ↑ |
ROS Levels | ↑ | ↓ |
Mitochondrial Proteins | ↓ Opa1, Mfn1, Mfn2 | ↑ Opa1, Mfn1, Mfn2 |
Western Blot: Detects TIMM44 at 45 kDa in human, mouse, and rat tissues .
Immunofluorescence: Localizes TIMM44 to the inner mitochondrial membrane .
Key Controls: siRNA knockdown (e.g., in U-2 OS cells) confirms specificity .
TIMM44 antibodies remain vital for studying mitochondrial disorders and angiogenesis-related pathologies. Ongoing research focuses on: