Samm50, a sorting and assembly machinery (SAM) complex protein, is an essential component of mitochondria. It is involved in protein sorting and assembly, and plays a key role in mitochondrial dynamics and quality control through regulating mitophagy. It also participates in maintaining cellular homeostasis by acting as a receptor for basal piecemeal mitophagy [2,5].

In cardiac hypertrophy, Samm50 was found to be a key positive regulator. Knockdown and overexpression studies in neonatal cardiomyocytes showed that overexpression of Samm50 promoted cardiac hypertrophy by regulating Pink1-Parkin-mediated mitophagy, while its knockdown had the opposite effect. Inhibition of mitophagy abolished the protective role of Samm50 deficiency against cardiac hypertrophy [1].

In non-alcoholic fatty liver disease (NAFLD), certain single nucleotide polymorphisms (SNPs) of SAMM50 (rs2073082, rs738491, rs3761472) were associated with an increased risk of the disease. In vitro studies indicated that SAMM50 gene polymorphisms decreased its expression, leading to increased lipid accumulation due to decreased fatty acid oxidation [3,6].

In beige adipocytes, knockdown of Samm50 repressed the expression of mitochondrial fusion genes and promoted that of fission genes, inhibiting the expression of thermogenic genes. Overexpression of Samm50 had the opposite effects, linking mitochondrial dynamics and thermogenesis [4].

In conclusion, Samm50 is crucial for mitochondrial function, playing important roles in processes like mitophagy, mitochondrial dynamics, and thermogenesis. Its dysregulation is associated with diseases such as cardiac hypertrophy and NAFLD. Gene knockout or knockdown models have been instrumental in revealing these functions, providing insights into potential therapeutic strategies for related diseases.