Investigating the role of the mitochondrial protein ATAD3B in breast cancer cell proliferation and migration

Mitochondria are essential organelles involved in a wide range of processes, including intermediary metabolism, calcium and redox homeostasis, immune responses, and cell death. The ATPase family AAA domain-containing protein 3 (ATAD3) comprises two mitochondrial proteins, ATAD3A and ATAD3B, localized to the inner mitochondrial membrane. ATAD3B is a primate-specific paralog of ATAD3A, generated by a gene duplication event and characterized by a unique 62-amino-acid C-terminal extension resulting from a point mutation in the ancestral ATAD3A stop codon. While ATAD3A has established roles in cristae biogenesis and mitochondrial translation, the biological function of ATAD3B remains poorly understood. Preliminary studies from our laboratory have shown that ATAD3B expression, normally restricted to pluripotent cells, is also detected in highly glycolytic cancer cell lines and promotes a metabolic switch in murine cell models through its C-terminal extension. To investigate whether and how ATAD3B contributes to tumorigenesis, we used stable breast cancer cell lines expressing either full-length ATAD3B or a mutant lacking the C-terminal extension and evaluated its effects on cell proliferation and wound closure using a wound-healing assay. Our data indicate that cells expressing full-length ATAD3B showed a trend toward faster wound closure; however, this difference did not reach statistical significance.