Slc25a34, a member of the mitochondrial solute carrier family 25, is involved in transporting molecules over the mitochondrial membrane [3]. It has been implicated in multiple biological processes and disease-related pathways, and genetic models are valuable for studying its functions.

In hepatocyte-specific Slc25a34 knockout mice, loss of Slc25a34 led to increased mitochondrial biogenesis, lipid synthesis, and ADP/ATP ratio in hepatocytes. In the knockout model on a chow diet, it modestly affected liver function with altered glucose metabolism being the most prominent defect. After 2 months on a fast-food diet, knockouts had increased lipid content and impaired glucose tolerance, suggesting its role in lipid and glucose homeostasis during non-alcoholic fatty liver disease (NAFLD) [1].

In colorectal cancer, SLC25A34 was reduced in tissues and cells, and overexpression of SLC25A34 repressed the malignant phenotype of CRC cells. NKRF inhibited SLC25A34 transcription, and MYLIP could degrade NKRF to activate SLC25A34 transcription, suppressing xenograft formation and lung metastases [2].

In conclusion, Slc25a34 plays a crucial role in mitochondrial respiration, bioenergetics, lipid and glucose metabolism, and may act as a suppressor in colorectal cancer. The Slc25a34 knockout mouse models have provided important insights into its functions in NAFLD and colorectal cancer, helping to understand the underlying mechanisms of these diseases and potentially offering new therapeutic targets.