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Mitochondrial import inner membrane translocase subunit TIM23 (TIM23) is a fundamental component of the TIM23 complex, the primary machinery for importing nuclear-encoded proteins into the mitochondrial matrix and inner membrane [UniProt: P55313]. It forms a voltage-gated channel that facilitates the translocation of proteins containing a mitochondrial targeting signal, a process driven by the membrane potential and ATP hydrolysis [PubMed: 21857667]. TIM23 is increasingly recognized as a therapeutic target in oncology because cancer cells often overexpress components of the mitochondrial import machinery to meet high metabolic demands and maintain mitochondrial integrity [PubMed: 30241606]. Furthermore, defects in TIM23-mediated import are implicated in neurodegenerative diseases, such as Parkinson's disease, where mitochondrial dysfunction is a hallmark [PubMed: 28823558]. Small molecule inhibitors, such as MB-10 (MitoBlock-10), have demonstrated the ability to disrupt this import process, leading to reduced cell viability in certain cancer models [PubMed: 21857667]. Despite its potential, the essential nature of TIM23 across all tissues poses significant safety concerns regarding systemic mitochondrial toxicity and off-target effects [PubMed: 31515464].
Inhibition of the TIM23 complex-mediated protein translocation into the mitochondrial matrix or inner membrane.
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