TIMM23-ERAL1 Axis: A novel regulator of mitochondrial apoptosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy of the digestive system characterized by increasing global incidence and mortality rates. Translocase of the Inner Mitochondrial Membrane 23 (TIMM23), a key component of the mitochondrial inner membrane translocase complex, plays a critical role in the import and localization of mitochondrial proteins. Elevated TIMM23 expression is significantly associated with poor prognosis in patients with HCC Conversely, TIMM23 downregulation was found to have induced apoptosis and significantly inhibited the proliferation, migration, and invasive potential of HCC cells both in vitro and in vivo. Furthermore, we have identified the functional interplay between TIMM23 and ERA G-protein-like 1 (ERAL1). TIMM23 knockdown markedly altered mitochondrial membrane potential and permeability, leading to a subsequent decrease in ERAL1 expression. ERAL1 interacts with Bcl-2-like protein 1 (Bcl-XL) during apoptosis. These findings collectively underscore the pivotal role of the TIMM23-ERAL1 axis in HCC progression, suggesting that the therapeutic targeting of TIMM23 may offer a promising strategy for HCC treatment.