TOMM22, the translocase of outer mitochondrial membrane 22, is the central receptor of the TOMM complex. It plays a crucial role in the recognition and translocation of mitochondrial precursor proteins, and is involved in TOMM complex assembly. It is essential for maintaining mitochondrial function as most mitochondrial proteins are nuclear-encoded and imported by the TOMM complex [2,5]. Genetic models, such as zebrafish mutants and knockdown models, have been valuable in studying its function [3,6].

In a skeletal muscle-specific Csnk2b/Ck2β-conditional knockout (cKO) mouse model, reduced phosphorylation of TOMM22 was observed. This led to abnormal mitochondrial function, with reduced muscle strength and abnormal metabolic activity in oxidative muscle fibers. CSNK2-mediated phosphorylation of TOMM22 changes its binding affinity for mitochondrial precursor proteins. Additionally, PINK1 accumulated, labeling abnormal mitochondria for mitophagy. Mitophagy could be normalized by introducing a phosphomimetic TOMM22 mutant [5]. In zebrafish, knockdown of tomm22 induced hepatocyte death. This model also showed that BECs contributed to hepatocytes and surviving hepatocytes became hybrid cells, and both the inhibition of Wnt/β-catenin signaling and macrophage ablation suppressed the formation of hybrid hepatocytes [3].

In conclusion, TOMM22 is vital for mitochondrial protein import and maintaining mitochondrial homeostasis. The CKO mouse model and zebrafish knockdown models have provided insights into its role in muscle and liver-related biological processes. These findings may contribute to understanding diseases related to mitochondrial dysfunction, such as statin-induced myopathy, pancreatic cancer, and potentially Parkinson's disease [1,2,4,5].