TOMM34, or Translocase of the outer mitochondrial membrane 34, is a component of the cytosolic complex with Hsp70/Hsp90 and plays a role in mitochondrial protein import [4]. It is associated with pathways such as oxidative phosphorylation, citric acid cycle, and metabolism of purine and several amino acids, and potentially involved in NOTCH-, MAPK-, and STAT3-signaling [4].

TOMM34 deficiency significantly impaired the type I interferon responses and NF-κB-mediated inflammation in various human/murine cell lines, murine bone marrow-derived macrophages and in vivo. Mechanistically, TOMM34 recruits TRAF6 to facilitate the K63-linked polyubiquitination of NEMO upon viral infection, promoting downstream NF-κB activation [2]. In cancer, knockdown of TOMM34 in OSCC cells decreased cell proliferation, migration, and invasion, damaged mitochondria, and increased intracellular ROS levels [1]. In hepatocellular carcinoma cells, disturbing the interaction between TOMM34 and ATP5B using Gboxin increased sensitivity to metformin and suppressed tumor progression in vitro and in vivo [3].

In conclusion, TOMM34 is crucial for mitochondrial protein import and is involved in multiple biological pathways. Its deficiency models have revealed its role in antiviral innate immunity and cancer-related processes such as cell proliferation, metastasis, and drug sensitivity, highlighting its potential as a therapeutic target in diseases like severe COVID-19, influenza, and various cancers [1,2,3].