OPA1-Exon4b modulates the migration and invasion of hepatocellular carcinoma cells by ATP regulation

Optic Atrophy 1 (OPA1), a mitochondrial inner protein, is involved in both mitochondrial fusion dynamic and cell apoptosis. OPA1 Exon4b (OPA1-Exon4b) was reported to be downregulated in hepatocellular carcinoma (HCC). However, the relationship between OPA1-Exon4b and HCC remains unclear. Here we demonstrated that OPA1-Exon4b is related with migration using genome-wide transcriptome profiling. OPA1-Exon4b overexpression suppresses the migration and invasion, and cellular ATP production in HCC cells. The inhibition of migration and invasion by OPA1-Exon4b overexpression could be rescued by ATP addition, showing that OPA1-Exon4b suppresses the migration and invasion by decreasing ATP. We further demonstrated OPA1 overexpression induces the enlargement of mtDNA nucleoids in HCC cells. Thus, our study demonstrated a key role of OPA1-Exon4b to regulate the migration and invasion in HCC, which could provide a new prospect for the clinical diagnosis and therapy of HCC.