A complex containing the integral membrane proteins Tim17 and Tim23 constitutes the import channel for preproteins containing amino-terminal hydrophilic presequences. This complex is associated with Tim44 which serves as an adaptor protein for the binding of mtHsp70 to the membrane. mtHsp70, a 70 kDa heat shock protein of the mitochondrial matrix, drives the ATP-dependent import reaction of the processed preprotein after cleavage of the presequence[2]. Tim44 is tightly associated with the inner mitochondrial membrane on the matrix side. The Tim44 C-Terminal Domain (CTD) functions as an Inner Mitochondrial Membrane (IMM) anchor that recruits the Presequence protein Associated Motor (PAM) to the TIM23 channel[3]. Tim44 plays multiple roles in mitochondrial protein import by recruiting Ssc1 and its J protein cochaperone to the translocon and coordinating their interactions to promote efficient protein translocation in vivo[4].Hsp70 chaperones interact with substrate proteins in a coordinated fashion that is regulated by nucleotides and enhanced by assisting cochaperones[5]. MitoBloCK-10 inhibits inner membrane(Tim)44 binding to the precursor and to Hsp70.MitoBloCK-10 is the first small molecule modulator to attenuate protein-associated motor (PAM) complex activity. MB-10 (100 μM) is a potential attenuator of protein import into mitochondria.MB-10 inhibits the import of substrates that use the TIM23 import pathway.MB-10 (0-100 μM) inhibits protein import into mammalian mitochondria[6].
MitoBloCK-10 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary bladder epithelial cells (priBEC)
25 μM
24 hours
No significant effect on cell viability and death
Cell Death Dis. 2024 Mar 11;15(3):204
T24 bladder cancer cells
25 μM
24 hours
Inhibited cell viability, proliferation, and motility, induced apoptosis
Cell Death Dis. 2024 Mar 11;15(3):204
hCMEC/D3
25μM
48 hours
MB-10 inhibited proliferation and migration in hCMEC/D3 cells, leading to mitochondrial dysfunction.
Cell Death Dis. 2023 May 5;14(5):307
hRMECs
25μM
48 hours
MB-10 inhibited proliferation and migration in hRMECs, leading to mitochondrial dysfunction.
Cell Death Dis. 2023 May 5;14(5):307
HUVECs
25μM
48 hours
MB-10 inhibited proliferation, migration, and in vitro capillary tube formation in HUVECs, leading to mitochondrial dysfunction, including reduced ATP and increased ROS production.
Cell Death Dis. 2023 May 5;14(5):307
MitoBloCK-10 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Bladder cancer xenograft model
Intraperitoneal injection
20 mg/kg
Every 48 hours for a total of three doses
Inhibited bladder cancer xenograft growth, induced oxidative stress, ATP reduction, and Akt-S6K1 inhibition
Cell Death Dis. 2024 Mar 11;15(3):204
C57BL/6 mice
Retinal angiogenesis model
Intravitreal injection
0.25 nM
Single injection, lasting 72 hours
MB-10 inhibited retinal angiogenesis in mice, leading to increased vascular leakage and acellular capillaries.
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