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Mitochondrial import receptor subunit TOM20 (TOM20) is a central component of the translocase of the outer mitochondrial membrane (TOM) complex, acting as the primary receptor for nuclear-encoded proteins destined for the mitochondria [1, 3]. It specifically recognizes and binds to the N-terminal mitochondrial targeting sequences (MTS) of precursor proteins, facilitating their delivery to the TOM40 translocation pore [7, 9]. Beyond its role in protein import, TOM20 is involved in critical cellular processes such as mitophagy, apoptosis regulation through interactions with BCL2 and BAX, and the maintenance of cellular redox balance [4, 8]. In various cancers, including prostate, colorectal, and chondrosarcoma, TOM20 is frequently overexpressed, where it promotes oxidative phosphorylation, metabolic reprogramming, and resistance to chemotherapy [5, 11, 14]. Conversely, its dysfunction or loss is associated with neurodegenerative diseases like Parkinson's disease, where it contributes to impaired mitochondrial quality control [2, 3]. Therapeutic interest in TOM20 involves its potential as a target for neuroprotective agents like SEV-SR3677 or as a sensitizer in cancer therapy [2, 13]. However, because of its essential role in mitochondrial biogenesis, pharmacological modulation of TOM20 poses significant challenges regarding systemic mitochondrial toxicity and cellular viability [15, 18].
Modulation of mitochondrial protein import and mitophagy; regulation of apoptosis and oxidative phosphorylation.
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